A STATus report on DC development

Journal of Leukocyte Biology

Volumn 92, Issue 3, 2012, Pages 445-459

  Li, Haiyan S ^a   Watowich, Stephanie S ^a,b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

Cytokines; Immune cell development; Transcription factors

Indexed keywords

CD103 ANTIGEN; CD86 ANTIGEN; COLONY STIMULATING FACTOR 1; CYTOKINE; FLT3 LIGAND; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERFERON; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; STAT PROTEIN; STAT1 PROTEIN; STAT2 PROTEIN; STAT3 PROTEIN; STAT5 PROTEIN; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR PU 1; TRANSCRIPTION FACTOR RUNX3; TRANSFORMING GROWTH FACTOR BETA1;

BONE MARROW; CELL DIFFERENTIATION; CELL LINE; CELL MATURATION; CELL POPULATION; CELL STRESS; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; GENE MUTATION; GENE OVEREXPRESSION; GENE PRODUCT; HUMAN; MACROPHAGE; MOLECULAR INTERACTION; NONHUMAN; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CYTOKINES; DENDRITIC CELLS; HUMANS; TRANSCRIPTION FACTORS;

EID: 84865509868     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0212052     Document Type: Review

References (240)

1. Steinman, R. M., Cohn, Z. A. (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J. Exp. Med. 139, 380-397.
2. Steinman, R. M., Cohn, Z. A. (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137, 1142-1162.
3. Liu, K., Nussenzweig, M. C. (2010) Origin and development of dendritic cells. Immunol. Rev. 234, 45-54.
4. Hashimoto, D., Miller, J., Merad, M. (2011) Dendritic cell and macrophage heterogeneity in vivo. Immunity 35, 323-335.
5. Shortman, K., Heath, W. R. (2010) The CD8+ dendritic cell subset. Immunol. Rev. 234, 18-31.
6. Reizis, B., Bunin, A., Ghosh, H. S., Lewis, K L., Sisirak, V. (2011) Plas-macytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29, 163-183.
7. Schmid, M. A., Kingston, D., Boddupalli, S., Manz, M. G. (2010) Instructive cytokine signals in dendritic cell lineage commitment. Immunol. Rev. 234, 32-44.
8. Merad, M., Manz, M. G. (2009) Dendritic cell homeostasis. Blood 113, 3418-3427.
9. Helft, J., Ginhoux, F., Bogunovic, M., Merad, M. (2010) Origin and functional heterogeneity of non-lymphoid tissue dendritic cells in mice. Immunol. Rev. 234, 55-75.
10. Cheng, P., Zhou, J., Gabrilovich, D. (2010) Regulation of dendritic cell differentiation and function by Notch and Wnt pathways. Immunol. Rev. 234, 105-119.
11. Romani, N., Clausen, B. E., Stoitzner, P. (2010) Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol. Rev. 234, 120-141.
12. Swiecki, M., Colonna, M. (2010) Unraveling the functions of plasmacy-toid dendritic cells during viral infections, autoimmunity, and tolerance. Immunol. Rev. 234, 142-162.
13. Dominguez, P. M., Ardavin, C. (2010) Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol. Rev. 234, 90-104.
14. Collin, M., Bigley, V., Haniffa, M., Hambleton, S. (2011) Human dendritic cell deficiency: the missing ID? Nat. Rev. Immunol. 11, 575-583.
15. Belz, G. T., Nutt, S. L. (2012) Transcriptional programming of the dendritic cell network. Nat. Rev. Immunol. 12, 101-113.
16. Cella, M., Jarrossay, D., Facchetti, F., Alebardi, O., Nakajima, H., Lanza-vecchia, A., Colonna, M. (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5, 919-923.
17. Siegal, F. P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P. A., Shah, K., Ho, S., Antonenko, S., Liu, Y. J. (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 18351837.
18. Asselin-Paturel, C., Boonstra, A., Dalod, M., Durand, I., Yessaad, N., Dezutter-Dambuyant, C., Vicari, A., O'Garra, A., Biron, C., Briere, F., Trinchieri, G. (2001) Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat. Immunol. 2, 1144-1150.
19. Contractor, N., Louten, J., Kim, L., Biron, C. A., Kelsall, B. L. (2007) Cutting edge: Peyer's patch plasmacytoid dendritic cells (pDCs) produce low levels of type I interferons: possible role for IL-10, TGF^, and prostaglandin E2 in conditioning a unique mucosal pDC phenotype. J. Immunol. 179, 26290-2694.
20. Nestle, F. O., Conrad, C., Tun-Kyi, A., Homey, B., Gombert, M., Boy-man, O., Burg, G., Liu, Y. J., Gilliet, M. (2005) Plasmacytoid preden-dritic cells initiate psoriasis through interferon-alpha production. J. Exp. Med. 202, 135-143.
21. Farkas, L., Beiske, K., Lund-Johansen, F., Brandtzaeg, P., Jahnsen, F. L. (2001) Plasmacytoid dendritic cells (natural interferon-a/^-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am. J. Pathol. 159, 237-243.
22. Jahnsen, F. L., Lund-Johansen, F., Dunne, J. F., Farkas, L., Haye, R., Brandtzaeg, P. (2000) Experimentally induced recruitment of plasma-cytoid (CD123high) dendritic cells in human nasal allergy. J. Immunol. 165, 4062-4068.
23. Wollenberg, A., Wagner, M., Gunther, S., Towarowski, A., Tuma, E., Moderer, M., Rothenfusser, S., Wetzel, S., Endres, S., Hartmann, G. (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J. Invest. Dermatol. 119, 1096-1102.
24. Bangert, C., Friedl, J., Stary, G., Stingl, G., Kopp, T. (2003) Immuno-pathologic features of allergic contact dermatitis in humans: participation of plasmacytoid dendritic cells in the pathogenesis of the disease? J. Invest. Dermatol. 121, 1409-1418.
25. Liu, Y. J. (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23, 275-306.
26. Reizis, B., Colonna, M., Trinchieri, G., Barrat, F., Gilliet, M. (2011) Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system? Nat. Rev. Immunol. 11, 558-565.
27. Lande, R., Gilliet, M. (2010) Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann. N. Y. Acad. Sci. 1183, 89-103.
28. Kadowaki, N., Antonenko, S., Lau, J. Y., Liu, Y. J. (2000) Natural interferon α/β-producing cells link innate and adaptive immunity. J. Exp. Med. 192, 219-226.
29. Takagi, H., Fukaya, T., Eizumi, K, Sato, Y., Sato, K, Shibazaki, A., Ot-suka, H., Hijikata, A., Watanabe, T., Ohara, O., Kaisho, T., Malissen, B. (2011) Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo. Immunity 35, 958-971.
30. Lanzavecchia, A., Sallusto, F. (2001) Regulation of T cell immunity by dendritic cells. Cell 106, 263-266.
31. Villadangos, J. A., Schnorrer, P. (2007) Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat. Rev. Immunol. 7, 543-555.
32. Pulendran, B., Tang, H., Denning, T. L. (2008) Division of labor, plasticity, and crosstalk between dendritic cell subsets. Curr. Opin. Immunol. 20, 61-67.
33. Rivollier, A., He, J., Kole, A., Valatas, V., Kelsall, B. L. (2012) Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J. Exp. Med. 209, 139-155.
34. Hume, D. A. (2008) Macrophages as APC and the dendritic cell myth. J. Immunol. 181, 5829-5835.
35. Hume, D. A. (2011) Applications of myeloid-specific promoters in transgenic mice support in vivo imaging and functional genomics but do not support the concept of distinct macrophage and dendritic cell lineages or roles in immunity. J. Leukoc. Biol. 89, 525-538.
36. Den Haan, J. M., Bevan, M. J. (2002) Constitutive versus activation-dependent cross-presentation of immune complexes by CD8+ and CD8 dendritic cells in vivo. J. Exp. Med. 196, 817-827.
37. Allan, R. S., Smith, C. M., Belz, G. T., van Lint, A. L., Wakim, L. M., Heath, W. R., Carbone, F. R. (2003) Epidermal viral immunity induced by CD8a+ dendritic cells but not by Langerhans cells. Science 301, 1925-1928.
38. Belz, G. T., Smith, C. M., Kleinert, L., Reading, P., Brooks, A., Short-man, K., Carbone, F. R., Heath, W. R. (2004) Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-re-stricted antigen presentation after lung infection with virus. Proc. Natl. Acad. Sci. U. S. A. 101, 8670-8675.
39. Kim, T. S., Braciale, T. J. (2009) Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS One 4, e4204.
40. Beauchamp, N. M., Busick, R. Y., Alexander-Miller, M. A. (2010) Functional divergence among CD103+ dendritic cell subpopulations following pulmonary poxvirus infection. J. Virol. 84, 10191-10199.
41. Bedoui, S., Whitney, P. G., Waithman, J., Eidsmo, L., Wakim, L., Caminschi, I., Allan, R. S., Wojtasiak, M., Shortman, K., Carbone, F. R., Brooks, A. G., Heath, W. R. (2009) Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol. 10, 488-495.
42. Del Rio, M. L., Bernhardt, G., Rodriguez-Barbosa, J. I., Forster, R. (2010) Development and functional specialization of CD103+ dendritic cells. Immunol. Rev. 234, 268-281.
43. Koski, G. K., Cohen, P. A., Roses, R. E., Xu, S., Czerniecki, B. J. (2008) Reengineering dendritic cell-based anti-cancer vaccines. Immunol. Rev. 222, 256-276.
44. D'Amico, A., Wu, L. (2003) The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J. Exp. Med. 198, 293-303.
45. Onai, N., Obata-Onai, A., Schmid, M. A., Ohteki, T., Jarrossay, D., Manz, M. G. (2007) Identification of clonogenic common Flt3 + M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat. Immunol. 8, 1207-1216.
46. Fogg, D. K., Sibon, C., Miled, C., Jung, S., Aucouturier, P., Littman, D. R., Cumano, A., Geissmann, F. (2006) A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311, 83-87.
47. Naik, S. H., Sathe, P., Park, H. Y., Metcalf, D., Proietto, A. I., Dakic, A., Carotta, S., O'Keeffe, M., Bahlo, M., Papenfuss, A., Kwak, J. Y., Wu, L., Shortman, K. (2007) Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat. Immunol. 8, 1217-1226.
48. Liu, K, Victora, G. D., Schwickert, T. A., Guermonprez, P., Meredith, M. M., Yao, K, Chu, F. F., Randolph, G. J., Rudensky, A. Y., Nussenz-weig, M. (2009) In vivo analysis of dendritic cell development and homeostasis. Science 324, 392-397.
49. Naik, S. H., Metcalf, D., van Nieuwenhuijze, A., Wicks, I., Wu, L., O'Keeffe, M., Shortman, K. (2006) Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat. Immunol. 7, 663671.
50. Waskow, C., Liu, K, Darrasse-Jeze, G., Guermonprez, P., Ginhoux, F., Merad, M., Shengelia, T., Yao, K, Nussenzweig, M. (2008) The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9, 676-683.
51. Liu, K, Waskow, C., Liu, X., Yao, K, Hoh, J., Nussenzweig, M. (2007) Origin of dendritic cells in peripheral lymphoid organs of mice. Nat. Immunol. 8, 578-583.
52. Geissmann, F., Prost, C., Monnet, J. P., Dy, M., Brousse, N., Hermine, O. (1998) Transforming growth factor β1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J. Exp. Med. 187, 961-966.
53. Randolph, G. J., Inaba, K, Robbiani, D. F., Steinman, R. M., Muller, W. A. (1999) Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11, 753-761.
54. Varol, C., Vallon-Eberhard, A., Elinav, E., Aychek, T., Shapira, Y., Luche, H., Fehling, H.J., Hardt, W. D., Shakhar, G., Jung, S. (2009) Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31, 502-512.
55. Merad, M., Ginhoux, F., Collin, M. (2008) Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8, 935-947.
56. Merad, M., Manz, M. G., Karsunky, H., Wagers, A., Peters, W., Charo, I., Weissman, I. L., Cyster, J. G., Engleman, E. G. (2002) Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3, 1135-1141.
57. Ginhoux, F., Tacke, F., Angeli, V., Bogunovic, M., Loubeau, M., Dai, X. M., Stanley, E. R., Randolph, G. J., Merad, M. (2006) Langerhans cells arise from monocytes in vivo. Nat. Immunol. 7, 265-273.
58. Shortman, K, Liu, Y. J. (2002) Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2, 151-161.
59. Ito, T., Liu, Y. J., Kadowaki, N. (2005) Functional diversity and plasticity of human dendritic cell subsets. Int. J. Hematol. 81, 188-196.
60. Wu, L., Liu, Y. J. (2007) Development of dendritic-cell lineages. Immunity 26, 741-750.
61. Ziegler-Heitbrock, L., Ancuta, P., Crowe, S., Dalod, M., Grau, V., Hart, D. N., Leenen, P. J., Liu, Y. J., MacPherson, G., Randolph, G. J., Scher-berich, J., Schmitz, J., Shortman, K, Sozzani, S., Strobl, H., Zembala, M., Austyn, J. M., Lutz, M. B. (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116, e74-80.
62. Dzionek, A., Fuchs, A., Schmidt, P., Cremer, S., Zysk, M., Miltenyi, S., Buck, D. W., Schmitz, J. (2000) BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J. Immunol. 165, 6037-6046.
63. MacDonald, K P., Munster, D. J., Clark, G. J., Dzionek, A., Schmitz, J., Hart, D. N. (2002) Characterization of human blood dendritic cell subsets. Blood 100, 4512-4520.
64. Lindstedt, M., Lundberg, K, Borrebaeck, C. A. (2005) Gene family clustering identifies functionally associated subsets of human in vivo blood and tonsillar dendritic cells. J. Immunol. 175, 4839-4846.
65. Segura, E., Valladeau-Guilemond, J., Donnadieu, M. H., Sastre-Garau, X., Soumelis, V., Amigorena, S. (2012) Characterization of resident and migratory dendritic cells in human lymph nodes. J. Exp. Med. 209, 653-660.
66. Doulatov, S., Notta, F., Eppert, K, Nguyen, L. T., Ohashi, P. S., Dick, J. E. (2010) Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat. Immunol. 11, 585-593.
67. Angel, C. E., Chen, C.J., Horlacher, O. C., Winkler, S., John, T., Browning, J., MacGregor, D., Cebon, J., Dunbar, P. R. (2009) Distinctive localization of antigen-presenting cells in human lymph nodes. Blood 113, 1257-1267.
68. McIlroy, D., Troadec, C., Grassi, F., Samri, A., Barrou, B., Autran, B., Debre, P., Feuillard, J., Hosmalin, A. (2001) Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors. Blood 97, 3470-3477.
69. Kadowaki, N., Ho, S., Antonenko, S., Malefyt, R. W., Kastelein, R. A., Bazan, F., Liu, Y. J. (2001) Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194, 863-869.
70. De Saint-Vis, B., Fugier-Vivier, I., Massacrier, C., Gaillard, C., Vanberv-liet, B., Ait-Yahia, S., Banchereau, J., Liu, Y. J., Lebecque, S., Caux, C. (1998) The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J. Immunol. 160, 1666-1676.
71. Poulin, L. F., Salio, M., Griessinger, E., Anjos-Afonso, F., Craciun, L., Chen, J. L., Keller, A. M., Joffre, O., Zelenay, S., Nye, E., Le Moine, A., Faure, F., Donckier, V., Sancho, D., Cerundolo, V., Bonnet, D., Reis e Sousa, C. (2010) Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8a+ dendritic cells. J. Exp. Med. 207, 1261-1271.
72. Bachem, A., Guttler, S., Hartung, E., Ebstein, F., Schaefer, M., Tan-nert, A., Salama, A., Movassaghi, K., Opitz, C., Mages, H. W., Henn, V., Kloetzel, P. M., Gurka, S., Kroczek, R. A. (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141 + cells as homologues of mouse CD8+ dendritic cells. J. Exp. Med. 207, 12731281.
73. Crozat, K, Guiton, R., Contreras, V., Feuillet, V., Dutertre, C. A., Ventre, E., Vu Manh, T. P., Baranek, T., Storset, A. K, Marvel, J., Boudi-not, P., Hosmalin, A., Schwartz-Cornil, I., Dalod, M. (2010) The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8a+ dendritic cells. J. Exp. Med. 207, 1283-1292.
74. Jongbloed, S. L., Kassianos, A. J., McDonald, K. J., Clark, G. J., Ju, X., Angel, C. E., Chen, C.J., Dunbar, P. R., Wadley, R. B., Jeet, V., Vulink, A. J., Hart, D. N., Radford, K.J. (2010) Human CD141+ (BDCA-3) + dendritic cells (DCs) represent a unique myeloid DC subset that crosspresents necrotic cell antigens. J. Exp. Med. 207, 1247-1260.
75. Nestle, F. O., Zheng, X. G., Thompson, C. B., Turka, L. A., Nickoloff, B. J. (1993) Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. J. Immunol. 151, 6535-6545.
76. Angel, C. E., Lala, A., Chen, C. J., Edgar, S. G., Ostrovsky, L. L., Dunbar, P. R. (2007) CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts. Int. Immunol. 19, 12711279.
77. Jaensson, E., Uronen-Hansson, H., Pabst, O., Eksteen, B., Tian, J., Coombes, J. L., Berg, P. L., Davidsson, T., Powrie, F., Johansson-Lind-bom, B., Agace, W. W. (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205, 2139-2149.
78. Collin, M. P., Hart, D. N., Jackson, G. H., Cook, G., Cavet, J., Mackinnon, S., Middleton, P. G., Dickinson, A. M. (2006) The fate of human Langerhans cells in hematopoietic stem cell transplantation. J. Exp. Med. 203, 27-33.
79. Haniffa, M., Ginhoux, F., Wang, X. N., Bigley, V., Abel, M., Dimmick, Bullock, S., Grisotto, M., Booth, T., Taub, P., Hilkens, C., Merad, M., Collin, M. (2009) Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation. J. Exp. Med. 206, 371-385.
80. Kanitakis, J., Morelon, E., Petruzzo, P., Badet, L., Dubernard, J. M. (2011) Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft. Exp. Dermatol. 20, 145-146.
81. Watowich, S. S., Liu, Y. J. (2010) Mechanisms regulating dendritic cell specification and development. Immunol. Rev. 238, 76-92.
82. Kingston, D., Schmid, M. A., Onai, N., Obata-Onai, A., Baumjohann, D., Manz, M. G. (2009) The concerted action of GM-CSF and Flt3-li-gand on in vivo dendritic cell homeostasis. Blood 114, 835-843.
83. McKenna, H. J., Stocking, K L., Miller, R. E., Brasel, K, De Smedt, T., Maraskovsky, E., Maliszewski, C. R., Lynch, D. H., Smith, J., Pulendran, B., Roux, E. R., Teepe, M., Lyman, S. D., Peschon, J. J. (2000) Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95, 3489-3497.
84. Naik, S. H., Proietto, A. I., Wilson, N. S., Dakic, A., Schnorrer, P., Fuchsberger, M., Lahoud, M. H., O'Keeffe, M., Shao, Q. X., Chen, W. F., Villadangos, J. A., Shortman, K, Wu, L. (2005) Cutting edge: Generation of splenic CD8+ and CD8-dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J. Immunol. 174, 6592-6597.
85. Maraskovsky, E., Brasel, K, Teepe, M., Roux, E. R., Lyman, S. D., Shortman, K, McKenna, H. J. (1996) Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184, 1953-1962.
86. O'Keeffe, M., Hochrein, H., Vremec, D., Pooley, J., Evans, R., Woulfe, Shortman, K. (2002) Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated gran-ulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice. Blood 99, 2122-2130.
87. Vollstedt, S., O'Keeffe, M., Odermatt, B., Beat, R., Glanzmann, B., Ri-esen, M., Shortman, K, Suter, M. (2004) Treatment of neonatal mice with Flt3 ligand leads to changes in dendritic cell subpopulations associated with enhanced IL-12 and IFN-alpha production. Eur. J. Immunol. 34, 1849-1860.
88. Choi, J. H., Cheong, C., Dandamudi, D. B., Park, C. G., Rodriguez, A., Mehandru, S., Velinzon, K, Jung, I. H., Yoo, J. Y., Oh, G. T., Steinman, R. M. (2011) Flt3 signaling-dependent dendritic cells protect against atherosclerosis. Immunity 35, 819-831.
89. Esashi, E., Wang, Y. H., Perng, O., Qin, X. F., Liu, Y. J., Watowich, S. S. (2008) The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 28, 509-520.
90. Inaba, K, Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S., Steinman, R. M. (1992) Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 176, 1693-1702.
91. Vremec, D., Lieschke, G. J., Dunn, A. R., Robb, L., Metcalf, D., Short-man, K. (1997) The influence of granulocyte/macrophage colony-stimulating factor on dendritic cell levels in mouse lymphoid organs. Eur. J. Immunol. 27, 40-44.
92. King, I. L., Kroenke, M. A., Segal, B. M. (2010) GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization. J. Exp. Med. 207, 953961.
93. Fancke, B., Suter, M., Hochrein, H., O'Keeffe, M. (2008) M-CSF: a novel plasmacytoid and conventional dendritic cell poietin. Blood 111, 150-159.
94. Borkowski, T. A., Letterio, J. J., Farr, A. G., Udey, M. C. (1996) A role for endogenous transforming growth factor β 1 in Langerhans cell biology: the skin of transforming growth factor β 1 null mice is devoid of epidermal Langerhans cells. J. Exp. Med. 184, 2417-2422.
95. Yoshida, H., Hayashi, S., Kunisada, T., Ogawa, M., Nishikawa, S., Oka-mura, H., Sudo, T., Shultz, L. D. (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345, 442-444.
96. Dai, X. M., Ryan, G. R., Hapel, A. J., Dominguez, M. G., Russell, R. G., Kapp, S., Sylvestre, V., Stanley, E. R. (2002) Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 99, 111-120.
97. Kabashima, K, Banks, T. A., Ansel, K M., Lu, T. T., Ware, C. F., Cys-ter, J. G. (2005) Intrinsic lymphotoxin-β receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity 22, 439-450.
98. Gilliet, M., Boonstra, A., Paturel, C., Antonenko, S., Xu, X. L., Trinchieri, G., O'Garra, A., Liu, Y. J. (2002) The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195, 953-958.
99. Cisse, B., Caton, M. L., Lehner, M., Maeda, T., Scheu, S., Locksley, R., Holmberg, D., Zweier, C., den Hollander, N. S., Kant, S. G., Holter, W., Rauch, A., Zhuang, Y., Reizis, B. (2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135, 37-48.
100. Carotta, S., Dakic, A., D'Amico, A., Pang, S. H., Greig, K. T., Nutt, S. L., Wu, L. (2010) The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity 32, 628-641.
101. Schiavoni, G., Mattei, F., Borghi, P., Sestili, P., Venditti, M., Morse, H. C., 3rd, Belardelli, F., Gabriele, L. (2004) ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells. Blood 103, 2221-2228.
102. Schiavoni, G., Mattei, F., Sestili, P., Borghi, P., Venditti, M., Morse, H. C., 3rd, Belardelli, F., Gabriele, L. (2002) ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8a+ dendritic cells. J. Exp. Med. 196, 1415-1425.
103. Tamura, T., Tailor, P., Yamaoka, K, Kong, H. J., Tsujimura, H., O'Shea, J. J., Singh, H., Ozato, K (2005) IFN regulatory factor-4 and-8 govern dendritic cell subset development and their functional diversity. J. Immunol. 174, 2573-2581.
104. Tsujimura, H., Tamura, T., Ozato, K (2003) Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. J. Immunol. 170, 1131-1135.
105. Laouar, Y., Welte, T., Fu, X. Y., Flavell, R. A. (2003) STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 19, 903912.
106. Li, H. S., Gelbard, A., Martinez, G. J., Esashi, E., Zhang, H., Nguyen-Jackson, H., Liu, Y. J., Overwijk, W. W., Watowich, S. S. (2011) Cell-intrinsic role for IFN-a-STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response. Blood 118, 3879-3889.
107. Hildner, K, Edelson, B. T., Purtha, W. E., Diamond, M., Matsushita, H., Kohyama, M., Calderon, B., Schraml, B. U., Unanue, E. R., Diamond, M. S., Schreiber, R. D., Murphy, T. L., Murphy, K. M. (2008) Batf3 deficiency reveals a critical role for CD8a+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097-1100.
108. Rathinam, C., Geffers, R., Yucel, R., Buer, J., Welte, K, Moroy, T., Klein, C. (2005) The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and function. Immunity 22, 717728.
109. Scott, E. W., Simon, M. C., Anastasi, J., Singh, H. (1994) Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265, 1573-1577.
110. Georgopoulos, K., Bigby, M., Wang, J. H., Molnar, A., Wu, P., Winandy, S., Sharpe, A. (1994) The Ikaros gene is required for the development of all lymphoid lineages. Cell 79, 143-156.
111. Anderson, K L., Perkin, H., Surh, C. D., Venturini, S., Maki, R. A., Torbett, B. E. (2000) Transcription factor PU.1 is necessary for development of thymic and myeloid progenitor-derived dendritic cells. J. Immunol. 164, 1855-1861.
112. Guerriero, A., Langmuir, P. B., Spain, L. M., Scott, E. W. (2000) PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells. Blood 95, 879-885.
113. Hacker, C., Kirsch, R. D., Ju, X. S., Hieronymus, T., Gust, T. C., Kuhl, C., Jorgas, T., Kurz, S. M., Rose-John, S., Yokota, Y., Zenke, M. (2003) Transcriptional profiling identifies Id2 function in dendritic cell development. Nat. Immunol. 4, 380-386.
114. Ghosh, H. S., Cisse, B., Bunin, A., Lewis, K L., Reizis, B. (2010) Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33, 905-916.
115. Jackson, J. T., Hu, Y., Liu, R., Masson, F., D'Amico, A., Carotta, S., Xin, A., Camilleri, M. J., Mount, A. M., Kallies, A., Wu, L., Smyth, G. K, Nutt, S. L., Belz, G. T. (2011) Id2 expression delineates differential checkpoints in the genetic program of CD8a+ and CD103+ dendritic cell lineages. EMBO J. 30, 2690-2704.
116. Edelson, B. T., Kc, W., Juang, R., Kohyama, M., Benoit, L. A., Klekotka, P. A., Moon, C., Albring, J. C., Ise, W., Michael, D. G., Bhattacharya, D., Stappenbeck, T. S., Holtzman, M. J., Sung, S. S., Murphy, T. L., Hildner, K, Murphy, K M. (2010) Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8a+ conventional dendritic cells. J. Exp. Med. 207, 823-836.
117. Bogunovic, M., Ginhoux, F., Helft, J., Shang, L., Hashimoto, D., Greter, M., Liu, K, Jakubzick, C., Ingersoll, M. A., Leboeuf, M., Stanley, E. R., Nussenzweig, M., Lira, S. A., Randolph, G. J., Merad, M. (2009) Origin of the lamina propria dendritic cell network. Immunity 31, 513-525.
118. Ginhoux, F., Liu, K., Helft, J., Bogunovic, M., Greter, M., Hashimoto, D., Price, J., Yin, N., Bromberg, J., Lira, S. A., Stanley, E. R., Nussenz-weig, M., Merad, M. (2009) The origin and development of nonlymphoid tissue CD103+ DCs. J. Exp. Med. 206, 3115-3130.
119. Honda, K., Mizutani, T., Taniguchi, T. (2004) Negative regulation of IFN-a/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells. Proc. Natl. Acad. Sci. U. S. A. 101, 2416-2421.
120. Suzuki, S., Honma, K., Matsuyama, T., Suzuki, K., Toriyama, K., Aki-toyo, I., Yamamoto, K., Suematsu, T., Nakamura, M., Yui, K., Kumatori, A. (2004) Critical roles of interferon regulatory factor 4 in CD11bhighCD8a-dendritic cell development. Proc. Natl. Acad. Sci. U. S. A. 101, 8981-8986.
121. Wu, L., D'Amico, A., Winkel, K D., Suter, M., Lo, D., Shortman, K (1998) RelB is essential for the development of myeloid-related CD8a-dendritic cells but not of lymphoid-related CD8a+ dendritic cells. Immunity 9, 839-847.
122. Caton, M. L., Smith-Raska, M. R., Reizis, B. (2007) Notch-RBP-J signaling controls the homeostasis of CD8-dendritic cells in the spleen. J. Exp. Med. 204, 1653-1664.
123. Fainaru, O., Woolf, E., Lotem, J., Yarmus, M., Brenner, O., Golden-berg, D., Negreanu, V., Bernstein, Y., Levanon, D., Jung, S., Groner, Y. (2004) Runx3 regulates mouse TGF^-mediated dendritic cell function and its absence results in airway inflammation. EMBO J. 23, 969-979.
124. Kel, J. M., Girard-Madoux, M. J., Reizis, B., Clausen, B. E. (2010) TGF-β is required to maintain the pool of immature Langerhans cells in the epidermis. J. Immunol. 185, 3248-3255.
125. Lyman, S. D., Jacobsen, S. E. (1998) c-kit ligand and Flt3 ligand: stem/ progenitor cell factors with overlapping yet distinct activities. Blood 91, 1101-1134.
126. Blom, B., Ho, S., Antonenko, S., Liu, Y. J. (2000) Generation of interferon a-producing predendritic cell (Pre-DC)2 from human CD34+ hematopoietic stem cells. J. Exp. Med. 192, 1785-1796.
127. Brasel, K., De Smedt, T., Smith, J. L., Maliszewski, C. R. (2000) Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures. Blood 96, 3029-3039.
128. Zhang, Y., Wang, Y., Ogata, M., Hashimoto, S., Onai, N., Matsushima, K. (2000) Development of dendritic cells in vitro from murine fetal liver-derived lineage phenotype-negative c-kit+ hematopoietic progenitor cells. Blood 95, 138-146.
129. Bjorck, P. (2001) Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice. Blood 98, 3520-3526.
130. Hochweller, K., Miloud, T., Striegler, J., Naik, S., Hammerling, G. J., Garbi, N. (2009) Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop. Blood 114, 4411-4421.
131. Karsunky, H., Merad, M., Cozzio, A., Weissman, I. L., Manz, M. G. (2003) Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J. Exp. Med. 198, 305-313.
132. Manfra, D.J., Chen, S. C., Jensen, K K., Fine, J. S., Wiekowski, M. T., Lira, S. A. (2003) Conditional expression of murine Flt3 ligand leads to expansion of multiple dendritic cell subsets in peripheral blood and tissues of transgenic mice. J. Immunol. 170, 2843-2852.
133. Sallusto, F., Lanzavecchia, A. (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor a. J. Exp. Med. 179, 11091118.
134. Caux, C., Vanbervliet, B., Massacrier, C., Dezutter-Dambuyant, C., de Saint-Vis, B., Jacquet, C., Yoneda, K., Imamura, S., Schmitt, D., Banchereau, J. (1996) CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF a. J. Exp. Med. 184, 695-706.
135. Palma, M., Adamson, L., Hansson, L., Kokhaei, P., Rezvany, R., Mellst-edt, H., Osterborg, A., Choudhury, A. (2008) Development of a dendritic cell-based vaccine for chronic lymphocytic leukemia. Cancer Immunol. Immunother. 57, 1705-1710.
136. Kadowaki, N., Kitawaki, T. (2011) Recent advance in antigen-specific immunotherapy for acute myeloid leukemia. Clin. Dev. Immunol. 2011, 104926.
137. Burgdorf, S. K, Fischer, A., Myschetzky, P. S., Munksgaard, S. B., Zocca, M. B., Claesson, M. H., Rosenberg, J. (2008) Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine. Oncol. Rep. 20, 1305-1311.
138. Zarei, S., Schwenter, F., Luy, P., Aurrand-Lions, M., Morel, P., Kopf, M., Dranoff, G., Mach, N. (2009) Role of GM-CSF signaling in cell-based tumor immunization. Blood 113, 6658-6668.
139. Soiffer, R., Hodi, F. S., Haluska, F., Jung, K, Gillessen, S., Singer, S., Tanabe, K, Duda, R., Mentzer, S., Jaklitsch, M., Bueno, R., Clift, S., Hardy, S., Neuberg, D., Mulligan, R., Webb, I., Mihm, M., Dranoff, G. (2003) Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J. Clin. Oncol. 21, 3343-3350.
140. Daro, E., Pulendran, B., Brasel, K, Teepe, M., Pettit, D., Lynch, D. H., Vremec, D., Robb, L., Shortman, K, McKenna, H. J., Maliszewski, C. R., Maraskovsky, E. (2000) Polyethylene glycol-modified GM-CSF expands CD11bhighCD11chigh but notCD11blowCD11chigh murine dendritic cells in vivo: a comparative analysis with Flt3 ligand. J. Immunol. 165, 49-58.
141. Hahm, B., Trifilo, M. J., Zuniga, E. I., Oldstone, M. B. (2005) Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling. Immunity 22, 247-257.
142. Zuniga, E. I., McGavern, D. B., Pruneda-Paz, J. L., Teng, C., Oldstone, M. B. (2004) Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. Nat. Immunol. 5, 1227-1234.
143. Swiecki, M., Wang, Y., Vermi, W., Gilfillan, S., Schreiber, R. D., Col-onna, M. (2011) Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J. Exp. Med. 208, 2367-2374.
144. Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., Tough, D. F. (2002) Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263-3271.
145. Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M., Matos, I., Kluger, C., Salazar, A. M., Colonna, M., Steinman, R. M. (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med. 206, 1589-1602.
146. Gonzalez-Navajas, J. M., Lee, J., David, M., Raz, E. (2012) Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 12, 125135.
147. Ichikawa, E., Hida, S., Omatsu, Y., Shimoyama, S., Takahara, K, Miya-gawa, S., Inaba, K, Taki, S. (2004) Defective development of splenic and epidermal CD4+ dendritic cells in mice deficient for IFN regulatory factor-2. Proc. Natl. Acad. Sci. U. S. A. 101, 3909-3914.
148. Franchini, M., Hefti, H., Vollstedt, S., Glanzmann, B., Riesen, M., Ack-ermann, M., Chaplin, P., Shortman, K, Suter, M. (2004) Dendritic cells from mice neonatally vaccinated with modified vaccinia virus Ankara transfer resistance against herpes simplex virus type I to naive one-week-old mice. J. Immunol. 172, 6304-6312.
149. Hamilton, J. A. (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 8, 533-544.
150. MacDonald, K P., Rowe, V., Bofinger, H. M., Thomas, R., Sasmono, T., Hume, D. A., Hill, G. R. (2005) The colony-stimulating factor 1 receptor is expressed on dendritic cells during differentiation and regulates their expansion. J. Immunol. 175, 1399-1405.
151. Nefedova, Y., Huang, M., Kusmartsev, S., Bhattacharya, R., Cheng, P., Salup, R., Jove, R., Gabrilovich, D. (2004) Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in Cancer J. Immunol. 172, 464-474.
152. Novak, U., Marks, D., Nicholson, S. E., Hilton, D., Paradiso, L. (1999) Differential ability of SOCS proteins to regulate IL-6 and CSF-1 induced macrophage differentiation. Growth Factors 16, 305-314.
153. Cao, X., Tay, A., Guy, G. R., Tan, Y. H. (1996) Activation and association of Stat3 with Src in v-Src-transformed cell lines. Mol. Cell. Biol. 16, 1595-1603.
154. Kaplan, D. H., Li, M. O., Jenison, M. C., Shlomchik, W. D., Flavell, R. A., Shlomchik, M.J. (2007) Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells. J. Exp. Med. 204, 2545-2552.
155. Kobie, J. J., Wu, R. S., Kurt, R. A., Lou, S., Adelman, M. K., Whitesell, L. J., Ramanathapuram, L. V., Arteaga, C. L., Akporiaye, E. T. (2003) Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res. 63, 1860-1864.
156. Yamaguchi, Y., Tsumura, H., Miwa, M., Inaba, K (1997) Contrasting effects of TGF-β! and TNF-a on the development of dendritic cells from progenitors in mouse bone marrow. Stem Cells 15, 144-153.
157. Van de Laar, L., van den Bosch, A., Wierenga, A. T., Janssen, H. L., Coffer, P. J., Woltman, A. M. (2011) Tight control of STAT5 activity determines human CD34-derived interstitial dendritic cell and Langerhans cell development. J. Immunol. 186, 7016-7024.
158. Cheers, C., Haigh, A. M., Kelso, A., Metcalf, D., Stanley, E. R., Young, A. M. (1988) Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granu-locyte-macrophage-, and multi-CSFs. Infect. Immun. 56, 247-251.
159. Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A., Pa-mer, E. G. (2003) TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19, 59-70.
160. Maraskovsky, E., Daro, E., Roux, E., Teepe, M., Maliszewski, C. R., Hoek, J., Caron, D., Lebsack, M. E., McKenna, H. J. (2000) In vivo generation of human dendritic cell subsets by Flt3 ligand. Blood 96, 878-884.
161. Rosenzwajg, M., Camus, S., Guigon, M., Gluckman, J. C. (1998) The influence of interleukin (IL)-4, IL-13, and Flt3 ligand on human dendritic cell differentiation from cord blood CD34+ progenitor cells Exp. Hematol. 26, 63-72.
162. Miller, J. S., McCullar, V., Punzel, M., Lemischka, I. R., Moore, K. A. (1999) Single adult human CD34+/Lin-/CD38-progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells Blood 93, 96-106.
163. Chen, W., Antonenko, S., Sederstrom, J. M., Liang, X., Chan, A. S., Kanzler, H., Blom, B., Blazar, B. R., Liu, Y. J. (2004) Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 103, 2547-2553.
164. Rickmann, M., Krauter, J., Stamer, K., Heuser, M., Salguero, G., Mis-chak-Weissinger, E., Ganser, A., Stripecke, R. (2011) Elevated frequencies of leukemic myeloid and plasmacytoid dendritic cells in acute myeloid leukemia with the FLT3 internal tandem duplication. Ann. Hema-tol. 90, 1047-1058.
165. Choudhary, C., Schwable, J., Brandts, C., Tickenbrock, L., Sargin, B., Kindler, T., Fischer, T., Berdel, W. E., Muller-Tidow, C., Serve, H. (2005) AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood 106, 265273.
166. Choudhary, C., Brandts, C., Schwable, J., Tickenbrock, L., Sargin, B., Ueker, A., Bohmer, F. D., Berdel, W. E., Muller-Tidow, C., Serve, H. (2007) Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Blood 110, 370-374.
167. Leischner, H., Albers, C., Grundler, R., Razumovskaya, E., Spieker-mann, K, Bohlander, S., Ronnstrand, L., Gotze, K., Peschel, C., Duys-ter, J. (2012) SRC is a signaling mediator in FLT3-ITD but not in FLT3-TKD positive AML. Blood doi:10.1182/blood-2011-07-365726 [Epub ahead of print].
168. Rocnik, J. L., Okabe, R., Yu, J. C., Lee, B. H., Giese, N., Schenkein, D. P., Gilliland, D. G. (2006) Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. Blood 108, 1339-1345.
169. Arima, K., Watanabe, N., Hanabuchi, S., Chang, M., Sun, S. C., Liu, Y. J. (2010) Distinct signal codes generate dendritic cell functional plasticity. Sci. Signal. 3, ra4.
170. Caux, C., Dezutter-Dambuyant, C., Schmitt, D., Banchereau, J. (1992) GM-CSF and TNF-a cooperate in the generation of dendritic Langer-hans cells. Nature 360, 258-261.
171. Szabolcs, P., Feller, E. D., Moore, M. A., Young, J. W. (1995) Progenitor recruitment and in vitro expansion of immunostimulatory dendritic cells from human CD34+ bone marrow cells by c-kit-ligand, GM-CSF, and TNF a. Adv. Exp. Med. Biol. 378, 17-20.
172. Steinman, R. M. (1996) Dendritic cells and immune-based therapies. Exp. Hematol. 24, 859-862.
173. McKenna, H. J. (2001) Role of hematopoietic growth factors/flt3 ligand in expansion and regulation of dendritic cells. Curr. Opin. Hema-tol. 8, 149-154.
174. Dranoff, G. (2002) GM-CSF-based cancer vaccines. Immunol. Rev. 188, 147-154.
175. Waller, E. K, Ernstoff, M. S. (2003) Modulation of antitumor immune responses by hematopoietic cytokines. Cancer 97, 1797-1809.
176. Cochran, A. J., Huang, R. R., Lee, J., Itakura, E., Leong, S. P., Essner, R. (2006) Tumour-induced immune modulation of sentinel lymph nodes. Nat. Rev. Immunol. 6, 659-670.
177. Draube, A., Klein-Gonzalez, N., Mattheus, S., Brillant, C., Hellmich, M., Engert, A., von Bergwelt-Baildon, M. (2011) Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PloS One 6, e18801.
178. Garcia, F., Climent, N., Assoumou, L., Gil, C., Gonzalez, N., Alcami, J., Leon, A., Romeu, J., Dalmau, J., Martinez-Picado, J., Lifson, J., Autran, B., Costagliola, D., Clotet, B., Gatell, J. M., Plana, M., Gallart, T. (2011) A therapeutic dendritic cell-based vaccine for HIV-1 infection. J. Infect. Dis. 203, 473-478.
179. Verkade, M. A., van de Wetering, J., Klepper, M., Vaessen, L. M., Weimar, W., Betjes, M. G. (2004) Peripheral blood dendritic cells and GM-CSF as an adjuvant for hepatitis B vaccination in hemodialysis patients. Kidney Int. 66, 614-621.
180. Wang, K., Nishimoto, K. P., Mehta, R. S., Nelson, E. L. (2006) An alternative flow cytometry strategy for peripheral blood dendritic cell enumeration in the setting of repetitive GM-CSF dosing. J. Transl. Med. 4, 18.
181. Sathaliyawala, T., O'Gorman, W. E., Greter, M., Bogunovic, M., Kon-jufca, V., Hou, Z. E., Nolan, G. P., Miller, M. J., Merad, M., Reizis, B. (2010) Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity 33, 597-606.
182. Zhang, S., Broxmeyer, H. E. (2000) Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2. and PI3 kinase. Biochem. Biophys. Res. Commun. 277, 195-199.
183. Zhang, S., Fukuda, S., Lee, Y., Hangoc, G., Cooper, S., Spolski, R., Leonard, W. J., Broxmeyer, H. E. (2000) Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J. Exp. Med. 192, 719-728.
184. Takeda, K, Noguchi, K, Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., Akira, S. (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl. Acad. Sci. U. S. A. 94, 3801-3804.
185. Melillo, J. A., Song, L., Bhagat, G., Blazquez, A. B., Plumlee, C. R., Lee, C., Berin, C., Reizis, B., Schindler, C. (2010) Dendritic cell (DC)-spe-cific targeting reveals Stat3 as a negative regulator of DC function. J. Immunol. 184, 2638-2645.
186. Teglund, S., McKay, C., Schuetz, E., van Deursen, J. M., Stravopodis, D., Wang, D., Brown, M., Bodner, S., Grosveld, G., Ihle, J. N. (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93, 841-850.
187. Cui, Y., Riedlinger, G., Miyoshi, K, Tang, W., Li, C., Deng, C. X., Robinson, G. W., Hennighausen, L. (2004) Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol. Cell. Biol. 24, 80378047.
188. Yao, Z., Cui, Y., Watford, W. T., Bream, J. H., Yamaoka, K., Hissong, B. D., Li, D., Durum, S. K, Jiang, Q., Bhandoola, A., Hennighausen, L., O'Shea, J. J. (2006) Stat5a/b are essential for normal lymphoid development and differentiation. Proc. Natl. Acad. Sci. U. S. A. 103, 10001005.
189. Meraz, M. A., White, J. M., Sheehan, K C., Bach, E. A., Rodig, S.J., Dighe, A. S., Kaplan, D. H., Riley, J. K, Greenlund, A. C., Campbell, D., Carver-Moore, K, DuBois, R. N., Clark, R., Aguet, M., Schreiber, R. D. (1996) Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84, 431-442.
190. Durbin, J. E., Hackenmiller, R., Simon, M. C., Levy, D. E. (1996) Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell 84, 443-450.
191. Biron, C. A. (2001) Interferons a and β as immune regulators-a new look. Immunity 14, 661-664.
192. Garcia-Sastre, A., Biron, C. A. (2006) Type 1 interferons and the virus-host relationship: a lesson in detente. Science 312, 879-882.
193. Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H., Schreiber, R. D. (1998) How cells respond to interferons. Annu. Rev. Biochem. 67, 227-264.
194. Darnell, J. E., Jr., Kerr, I. M., Stark, G. R. (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415-1421.
195. Van Boxel-Dezaire, A. H., Rani, M. R., Stark, G. R. (2006) Complex modulation of cell type-specific signaling in response to type I interferons. Immunity 25, 361-372.
196. Dong, C. (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 8, 337-348.
197. Zhu, J., Paul, W. E. (2010) Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 238, 247-262.
198. Rothenberg, E. V. (2011) T cell lineage commitment: identity and renunciation. J. Immunol. 186, 6649-6655.
199. Lawrence, T., Natoli, G. (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat. Rev. Immunol. 11, 750-761.
200. Dore, L. C., Crispino, J. D. (2011) Transcription factor networks in ery-throid cell and megakaryocyte development. Blood 118, 231-239.
201. Orkin, S. H. (2000) Diversification of haematopoietic stem cells to specific lineages. Nat. Rev. Genet. 1, 57-64.
202. Rosenbauer, F., Tenen, D. G. (2007) Transcription factors in myeloid development: balancing differentiation with transformation. Nat. Rev. Immunol. 7, 105-117.
203. Tenen, D. G., Hromas, R., Licht, J. D., Zhang, D. E. (1997) Transcription factors, normal myeloid development, and leukemia. Blood 90,
204. Rosenbauer, F., Koschmieder, S., Steidl, U., Tenen, D. G. (2005) Effect of transcription-factor concentrations on leukemic stem cells. Blood 106, 1519-1524.
205. Onai, N., Obata-Onai, A., Tussiwand, R., Lanzavecchia, A., Manz, M. G. (2006) Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. J. Exp. Med. 203, 227-238.
206. McKercher, S. R., Torbett, B. E., Anderson, K. L., Henkel, G. W., Vestal, D. J., Baribault, H., Klemsz, M., Feeney, A. J., Wu, G. E., Paige, C. J., Maki, R. A. (1996) Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15, 5647-5658.
207. Rosenbauer, F., Wagner, K, Kutok, J. L., Iwasaki, H., Le Beau, M. M., Okuno, Y., Akashi, K, Fiering, S., Tenen, D. G. (2004) Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat. Genet. 36, 624-630.
208. Dakic, A., Metcalf, D., Di Rago, L., Mifsud, S., Wu, L., Nutt, S. L. (2005) PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis. J. Exp. Med. 201, 1487-1502.
209. Bakri, Y., Sarrazin, S., Mayer, U. P., Tillmanns, S., Nerlov, C., Boned, A., Sieweke, M. H. (2005) Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate. Blood 105, 2707-2716.
210. Laiosa, C. V., Stadtfeld, M., Xie, H., de Andres-Aguayo, L., Graf, T. (2006) Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBPa and PU.1 transcription factors. Immunity 25, 731-744.
211. Panopoulos, A. P., Bartos, D., Zhang, L., Watowich, S. S. (2002) Control of myeloid-specific integrin aMb2 (CD11b/CD18) expression by cytokines is regulated by Stat3-dependent activation of PU.1. J. Biol. Chem. 277, 19001-19007.
212. Hegde, S., Ni, S., He, S., Yoon, D., Feng, G. S., Watowich, S. S., Paulson, R. F., Hankey, P. A. (2009) Stat3 promotes the development of erythroleukemia by inducing PU.1 expression and inhibiting ery-throid differentiation. Oncogene 28, 3349-3359.
213. Holtschke, T., Lohler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., Lou, J., Knobeloch, K. P., Gabriele, L., Waring, J. F., Bachmann, M. F., Zinkernagel, R. M., Morse, H. C., 3rd, Ozato, K., Horak, I. (1996) Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell 87, 307-317.
214. Becker, A. M., Michael, D. G., Satpathy, A. T., Sciammas, R., Singh, H., Bhattacharya, D. (2012) IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors. Blood 119, 2003-2012.
215. Tailor, P., Tamura, T., Morse, H. C., 3rd, Ozato, K (2008) The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111, 1942-1945.
216. Hambleton, S., Salem, S., Bustamante, J., Bigley, V., Boisson-Dupuis, S., Azevedo, J., Fortin, A., Haniffa, M., Ceron-Gutierrez, L., Bacon, C. M., Menon, G., Trouillet, C., McDonald, D., Carey, P., Ginhoux, F., Alsina, L., Zumwalt, T. J., Kong, X. F., Kumararatne, D., Butler, K, Hubeau, M., Feinberg, J., Al-Muhsen, S., Cant, A., Abel, L., Chaussabel, D., Doffinger, R., Talesnik, E., Grumach, A., Duarte, A., Abarca, K, Mo-raes-Vasconcelos, D., Burk, D., Berghuis, A., Geissmann, F., Collin, M., Casanova, J. L., Gros, P. (2011) IRF8 mutations and human dendriticcell immunodeficiency. N. Engl. J. Med. 365, 127-138.
217. Kanno, Y., Kozak, C. A., Schindler, C., Driggers, P. H., Ennist, D. L., Gleason, S. L., Darnell, J. E., Jr., Ozato, K (1993) The genomic structure of the murine ICSBP gene reveals the presence of the y interferon-responsive element, to which an ISGF3 a subunit (or similar) molecule binds. Mol. Cell. Biol. 13, 3951-3963.
218. Schmidt, M., Nagel, S., Proba, J., Thiede, C., Ritter, M., Waring, J. F., Rosenbauer, F., Huhn, D., Wittig, B., Horak, I., Neubauer, A. (1998) Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood 91, 22-29.
219. Lehtonen, A., Lund, R., Lahesmaa, R., Julkunen, I., Sareneva, T., Ma-tikainen, S. (2003) IFN-a and IL-12 activate IFN regulatory factor 1 (IRF-1), IRF-4, and IRF-8 gene expression in human NK and T cells. Cytokine 24, 81-90.
220. Yang, C. Y., Best, J. A., Knell, J., Yang, E., Sheridan, A. D., Jesionek, A. K., Li, H. S., Rivera, R. R., Lind, K C., D'Cruz, L. M., Watowich, S. S., Murre, C., Goldrath, A. W. (2011) The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat. Immunol. 12, 1221-1229.
221. Bigley, V., Haniffa, M., Doulatov, S., Wang, X. N., Dickinson, R., McGovern, N., Jardine, L., Pagan, S., Dimmick, I., Chua, I., Wallis, J., Lordan, J., Morgan, C., Kumararatne, D. S., Doffinger, R., van der Burg, M., van Dongen, J., Cant, A., Dick, J. E., Hambleton, S., Collin, M. (2011) The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J. Exp. Med. 208, 227-234.
222. Hsu, A. P., Sampaio, E. P., Khan, J., Calvo, K R., Lemieux, J. E., Patel, S. Y., Frucht, D. M., Vinh, D. C., Auth, R. D., Freeman, A. F., Olivier, K N., Uzel, G., Zerbe, C. S., Spalding, C., Pittaluga, S., Raffeld, M., Kuhns, D. B., Ding, L., Paulson, M. L., Marciano, B. E., Gea-Bana-cloche, J. C., Orange, J. S., Cuellar-Rodriguez, J., Hickstein, D. D., Holland, S. M. (2011) Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 118, 2653-2655.
223. Dickinson, R. E., Griffin, H., Bigley, V., Reynard, L. N., Hussain, R., Haniffa, M., Lakey, J. H., Rahman, T., Wang, X. N., McGovern, N., Pagan, S., Cookson, S., McDonald, D., Chua, I., Wallis, J., Cant, A., Wright, M., Keavney, B., Chinnery, P. F., Loughlin, J., Hambleton, S., Santibanez-Koref, M., Collin, M. (2011) Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood. 118, 2656-2658.
224. Tsai, F. Y., Orkin, S. H. (1997) Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 89, 3636-3643.
225. Rodrigues, N. P., Janzen, V., Forkert, R., Dombkowski, D. M., Boyd, A. S., Orkin, S. H., Enver, T., Vyas, P., Scadden, D. T. (2005) Haploin-sufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis. Blood 106, 477-484.
226. Vicente, C., Conchillo, A., Garcia-Sanchez, M. A., Odero, M. D. (2011) The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit. Rev. Oncol Hematol. 82, 1-17.
227. Fujiwara, T., O'Geen, H., Keles, S., Blahnik, K, Linnemann, A. K, Kang, Y. A., Choi, K, Farnham, P. J., Bresnick, E. H. (2009) Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. Mol. Cell 36, 667-681.
228. Wilson, N. K, Foster, S. D., Wang, X., Knezevic, K, Schutte, J., Kaima-kis, P., Chilarska, P. M., Kinston, S., Ouwehand, W. H., Dzierzak, E., Pimanda, J. E., de Bruijn, M. F., Gottgens, B. (2010) Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 7, 532544.
229. Zhang, P., Behre, G., Pan, J., Iwama, A., Wara-Aswapati, N., Radomska, H. S., Auron, P. E., Tenen, D. G., Sun, Z. (1999) Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc. Natl. Acad. Sci. U. S. A. 96, 8705-8710.
230. Minegishi, Y., Saito, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pasic, S., Stojkovic, O., Metin, A., Karasuyama, H. (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448, 1058-1062.
231. He, J. L., Liu, J. H., Liu, F., Tan, P., Lin, T., Li, X. L. (2012) Mutation screening of BMP4 and Id2 genes in Chinese patients with congenital ureteropelvic junction obstruction. Eur. J. Pediatr. 171, 451-456.
232. Nagasawa, M., Schmidlin, H., Hazekamp, M. G., Schotte, R., Blom, B. (2008) Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B. Eur. J. Immunol. 38, 2389-2400.
233. Saito, M., Nagasawa, M., Takada, H., Hara, T., Tsuchiya, S., Agematsu, K, Yamada, M., Kawamura, N., Ariga, T., Tsuge, I., Nonoyama, S., Karasuyama, H., Minegishi, Y. (2011) Defective IL-10 signaling in hy-per-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells. J. Exp. Med. 208, 235-249.
234. Giacomelli, M., Tamassia, N., Moratto, D., Bertolini, P., Ricci, G., Bertulli, C., Plebani, A., Cassatella, M., Bazzoni, F., Badolato, R. (2011) SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function. Eur. J. Immunol. 41, 3075-3084.
235. Murray, P. J. (2006) Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr. Opin. Pharmacol. 6, 379-386.
236. Spits, H., Couwenberg, F., Bakker, A. Q., Weijer, K, Uittenbogaart, C. H. (2000) Id2 and Id3 inhibit development of CD34+ stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J. Exp. Med. 192, 1775-1784.
237. Schotte, R., Nagasawa, M., Weijer, K, Spits, H., Blom, B. (2004) The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J. Exp. Med. 200, 1503-1509.
238. Allman, D., Dalod, M., Asselin-Paturel, C., Delale, T., Robbins, S. H., Trinchieri, G., Biron, C. A., Kastner, P., Chan, S. (2006) Ikaros is required for plasmacytoid dendritic cell differentiation. Blood 108, 40254034.
239. Wu, L., Nichogiannopoulou, A., Shortman, K, Georgopoulos, K (1997) Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity 7, 483-492.
240. Aliberti, J., Schulz, O., Pennington, D. J., Tsujimura, H., Reis e Sousa, C., Ozato, K, Sher, A. (2003) Essential role for ICSBP in the in vivo development of murine CD8a+ dendritic cells. Blood 101, 305-310.