Plasmacytoid dendritic cells: Recent progress and open questions

Annual Review of Immunology

Volumn 29, Issue , 2011, Pages 163-183

  Reizis, Boris ^a   Bunin, Anna ^a   Ghosh, Hiyaa S ^a   Lewis, Kanako L ^a   Sisirak, Vanja ^a  

^a NewYork Presbyterian Hospital   (United States)

Author keywords

antigen presentation; dendritic cells; innate immunity; type I interferon

Indexed keywords

FLT3 LIGAND; INTERFERON; INTERFERON REGULATORY FACTOR 7; TOLL LIKE RECEPTOR;

ARTICLE; AUTOIMMUNE DISEASE; CELL ACTIVATION; CELL FATE; CELL FUNCTION; CELL SURVIVAL; CYTOLOGY; DENDRITIC CELL; HUMAN; NONHUMAN; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; T LYMPHOCYTE; VIRUS IMMUNITY;

ANIMALS; AUTOIMMUNE DISEASES; CELL LINEAGE; DENDRITIC CELLS; HUMANS; INFECTION; SIGNAL TRANSDUCTION;

EID: 79953059788     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-031210-101345     Document Type: Article

References (152)

1. Liu YJ. 2005. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23:275-306.
2. Villadangos JA, Young L. 2008. Antigen-presentation properties of plasmacytoid dendritic cells. Immunity 29:352-61.
3. Gilliet M, Cao W, Liu YJ. 2008. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat. Rev. Immunol. 8:594-606.
4. Jegalian AG, Facchetti F, Jaffe ES. 2009. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv. Anat. Pathol. 16:392-404.
5. Swiecki M, Colonna M. 2010. Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance. Immunol. Rev. 234:142-62.
6. Reizis B. 2010. Regulation of plasmacytoid dendritic cell development. Curr. Opin. Immunol. 22:206-11.
7. Sozzani S, Vermi W, Del Prete A, Facchetti F. 2010. Trafficking properties of plasmacytoid dendritic cells in health and disease. Trends Immunol. 31:270-77.
8. Ronnblom L, Ramstedt U, Alm GV. 1983. Properties of human natural interferon-producing cells stimulated by tumor cell lines. Eur. J. Immunol. 13:471-76. (Pubitemid 13060111)
9. Sandberg K, Eloranta ML, Johannisson A, Alm GV. 1991. Flow cytometric analysis of natural interferon-αproducing cells. Scand. J. Immunol. 34:565-76.
10. Feldman M, Fitzgerald-Bocarsly P. 1990. Sequential enrichment and immunocytochemical visualization of human interferon-α-producing cells. J. Interferon Res. 10:435-46. (Pubitemid 20244769)
11. Fitzgerald-Bocarsly P. 1993. Human natural interferon-αproducing cells. Pharmacol. Ther. 60:39-62.
12. Chehimi J, Starr SE, Kawashima H, Miller DS, Trinchieri G, et al. 1989. Dendritic cells and IFN-α-producing cells are two functionally distinct non-B, non-monocytic HLA-DR+ cell subsets in human peripheral blood. Immunology 68:486-90. (Pubitemid 20010005)
13. Starr SE, Bandyopadhyay S, Shanmugam V, Hassan N, Douglas S, et al. 1993. Morphological and functional differences between HLA-DR+ peripheral blood dendritic cells andHLA-DR+ IFN-αproducing cells. Adv. Exp. Med. Biol. 329:173-78. (Pubitemid 23199620)
14. Facchetti F, de Wolf-Peeters C, Mason DY, Pulford K, van denOord JJ, Desmet VJ. 1988. Plasmacytoid Tcells. Immunohistochemical evidence for theirmonocyte/macrophage origin.Am. J. Pathol. 133:15-21.
15. Facchetti F, De Wolf-Peeters C, Kennes C, Rossi G, De Vos R, et al. 1990. Leukemia-associated lymph node infiltrates of plasmacytoid monocytes (so-called plasmacytoid T-cells). Evidence for two distinct histological and immunophenotypical patterns. Am. J. Surg. Pathol. 14:101-12. (Pubitemid 20039005)
16. Vollenweider R, Lennert K. 1983. Plasmacytoid T-cell clusters in non-specific lymphadenitis. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 44:1-14. (Pubitemid 13007556)
17. Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ. 1997. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185:1101-11. (Pubitemid 27136802)
18. Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, et al. 1999. The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835-37.
19. Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, et al. 1999. Plasmacytoid monocytesmigrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5:919-23. (Pubitemid 29372419)
20. Bjorck P. 2001. Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice. Blood 98:3520-26.
21. Nakano H, Yanagita M, Gunn MD. 2001. CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194:1171-78. (Pubitemid 32995786)
22. Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, et al. 2001. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat. Immunol. 2:1144-50. (Pubitemid 33130149)
23. Blom B, Ho S, Antonenko S, Liu YJ. 2000. Generation of interferon α-producing predendritic cell (pre-DC)2 from human CD34+ hematopoietic stem cells. J. Exp. Med. 192:1785-96.
24. Gilliet M, Boonstra A, Paturel C, Antonenko S, Xu XL, et al. 2002. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195:953-58. (Pubitemid 34286765)
25. Crozat K, Guiton R, Guilliams M, Henri S, Baranek T, et al. 2010. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol. Rev. 234:177-98.
26. Luber CA, Cox J, Lauterbach H, Fancke B, Selbach M, et al. 2010. Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. Immunity 32:279-89.
27. Randolph GJ, Ochando J, Partida-Sanchez S. 2008. Migration of dendritic cell subsets and their precursors. Annu. Rev. Immunol. 26:293-316. (Pubitemid 351600378)
28. O'Keeffe M, Hochrein H, Vremec D, Caminschi I, Miller JL, et al. 2002. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate intoCD8+ dendritic cells only after microbial stimulus. J. Exp. Med. 196:1307-19. (Pubitemid 35375550)
29. 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. 8:578-83. (Pubitemid 46785121)
30. Steinman RM, Cohn ZA. 1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137:1142-62.
31. Asselin-Paturel C, Brizard G, Pin JJ, Briere F, Trinchieri G. 2003. Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody. J. Immunol. 171:6466-77. (Pubitemid 37532075)
32. Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, et al. 2008. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135:37-48.
33. Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K, et al. 2007. Alveolar macrophages are the primary interferon-αproducer in pulmonary infection with RNA viruses. Immunity 27:240-52. (Pubitemid 47284930)
34. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, et al. 2004. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 21:107-19. (Pubitemid 38925271)
35. Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. 2003. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19:225-34. (Pubitemid 37011337)
36. Caminschi I, Ahmet F, Heger K, Brady J, Nutt SL, et al. 2007. Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells. J. Exp. Med. 204:2579-90. (Pubitemid 350044784)
37. Blasius AL, Barchet W, Cella M, Colonna M. 2007. Development and function of murine B220+CD11c+NK1.1+ cells identify them as a subset of NK cells. J. Exp. Med. 204:2561-68. (Pubitemid 350044782)
38. Segura E, Wong J, Villadangos JA. 2009. Cutting edge:B220+CCR9-dendritic cells are not plasmacytoid dendritic cells but are precursors of conventional dendritic cells. J. Immunol. 183:1514-17.
39. Blasius AL, Giurisato E, Cella M, Schreiber RD, Shaw AS, Colonna M. 2006. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. J. Immunol. 177:3260-65. (Pubitemid 44277845)
40. Mach N, Gillessen S, Wilson SB, Sheehan C, Mihm M, Dranoff G. 2000. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res. 60:3239-46. (Pubitemid 30407923)
41. Cervantes-Barragan L, Kalinke U, Zust R, Konig M, Reizis B, et al. 2009. Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection. J. Immunol. 182:1099-106.
42. Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, et al. 2007. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat. Immunol. 8:1217-26. (Pubitemid 350011760)
43. Onai N, Obata-Onai A, Schmid MA, Ohteki T, Jarrossay D, Manz MG. 2007. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat. Immunol. 8:1207-16. (Pubitemid 350011759)
44. Sitnicka E, Bryder D, Theilgaard-Monch K, Buza-Vidas N, Adolfsson J, Jacobsen SE. 2002. Key role of flt3 ligand in regulation of the common lymphoid progenitor but not inmaintenance of the hematopoietic stem cell pool. Immunity 17:463-72. (Pubitemid 35223535)
45. Shigematsu H, Reizis B, Iwasaki H, Mizuno S, Hu D, et al. 2004. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity 21:43-53. (Pubitemid 38925266)
46. Corcoran L, Ferrero I, Vremec D, Lucas K, Waithman J, et al. 2003. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. J. Immunol. 170:4926-32. (Pubitemid 36554721)
47. Pelayo R, Hirose J, Huang J, Garrett KP, Delogu A, et al. 2005. Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. Blood 105:4407-15. (Pubitemid 40720788)
48. Welner RS, Esplin BL, Garrett KP, Pelayo R, Luche H, et al. 2009. Asynchronous RAG-1 expression during B lymphopoiesis. J. Immunol. 183:7768-77.
49. CatonML, Smith-RaskaMR, Reizis B. 2007. Notch-RBP-J signaling controls the homeostasis of CD8? dendritic cells in the spleen. J. Exp. Med. 204:1653-64. (Pubitemid 47048031)
50. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, et al. 2009. In vivo analysis of dendritic cell development and homeostasis. Science 324:392-97.
51. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. 2010. Development of monocytes, macrophages, and dendritic cells. Science 327:656-61.
52. Schmid MA, Kingston D, Boddupalli S, Manz MG. 2010. Instructive cytokine signals in dendritic cell lineage commitment. Immunol. Rev. 234:32-44.
53. Waskow C, Liu K, Darrasse-Jeze G, Guermonprez P, Ginhoux F, et al. 2008. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9:676-83. (Pubitemid 351712638)
54. Eidenschenk C, Crozat K, Krebs P, Arens R, Popkin D, et al. 2010. Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells. Proc. Natl. Acad. Sci. USA 107:9759-64.
55. Sathaliyawala T, O'Gorman WE, Greter M, Bogunovic M, Konjufca V, et al. 2010. Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity 33:597-606.
56. Vollstedt S, O'Keeffe M, Odermatt B, Beat R, Glanzmann B, et al. 2004. Treatment of neonatal mice with Flt3 ligand leads to changes in dendritic cell subpopulations associated with enhanced IL-12 and IFN-αproduction. Eur. J. Immunol. 34:1849-60. (Pubitemid 39256067)
57. Ghosh HS, Cisse B, Bunin A, Lewis KL, Reizis B. 2010. Continuous expression of E2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33:905-16.
58. Cao W, Bover L, Cho M, Wen X, Hanabuchi S, et al. 2009. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J. Exp. Med. 206:1603-14.
59. Robbins SH, Walzer T, Dembele D, Thibault C, Defays A, et al. 2008. Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol. 9:R17.
60. Bar-On L, Birnberg T, Kewis KL, Edelson B, Bruder D, et al. 2010. CX3CR1+ CD8α+ dendritic cells: a steady state population related to plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 107:14745-50.
61. Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, et al. 2009. Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139:1130-42.
62. Li P, Burke S, Wang J, Chen X, Ortiz M, et al. 2010. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science 329:85-89.
63. Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, et al. 2010. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367-70.
64. Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban JF Jr, et al. 2010. IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses. Nature 464:1362-66.
65. Takeuchi O, Akira S. 2009. Innate immunity to virus infection. Immunol. Rev. 227:75-86.
66. Pascale F, Contreras V, Bonneau M, Courbet A, Chilmonczyk S, et al. 2008. Plasmacytoid dendritic cells migrate in afferent skin lymph. J. Immunol. 180:5963-72.
67. Diebold SS, Montoya M, Unger H, Alexopoulou L, Roy P, et al. 2003. Viral infection switches nonplasmacytoid dendritic cells into high interferon producers. Nature 424:324-28. (Pubitemid 36899375)
68. Iwakoshi NN, Pypaert M, Glimcher LH. 2007. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J. Exp. Med. 204:2267-75. (Pubitemid 47529314)
69. Barchet W, Cella M, Odermatt B, Asselin-Paturel C, Colonna M, Kalinke U. 2002. Virus-induced interferon αproduction by a dendritic cell subset in the absence of feedback signaling in vivo. J. Exp. Med. 195:507-16. (Pubitemid 34461303)
70. Kerkmann M, Rothenfusser S, Hornung V, Towarowski A, Wagner M, et al. 2003. Activation with CpG-A and CpG-B oligonucleotides reveals two distinct regulatory pathways of type I IFN synthesis in human plasmacytoid dendritic cells. J. Immunol. 170:4465-74. (Pubitemid 36519951)
71. Izaguirre A, Barnes BJ, Amrute S, Yeow WS, Megjugorac N, et al. 2003. Comparative analysis of IRF and IFN-αexpression in human plasmacytoid and monocyte-derived dendritic cells. J. Leukoc. Biol. 74:1125-38. (Pubitemid 38040335)
72. Blasius AL, Arnold CN, Georgel P, Rutschmann S, Xia Y, et al. 2010. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA. 107:19973-78.
73. Kumagai Y, Kumar H, Koyama S, Kawai T, Takeuchi O, Akira S. 2009. Cutting edge: TLR-dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-αproduction in plasmacytoid dendritic cells. J. Immunol. 182:3960-64.
74. Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, et al. 2005. Spatiotemporal regulation ofMyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434:1035-40. (Pubitemid 40586053)
75. Kim T, Pazhoor S, Bao M, Zhang Z, Hanabuchi S, et al. 2010. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 107:15181-86.
76. Guiducci C, Ott G, Chan JH, Damon E, Calacsan C, et al. 2006. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J. Exp. Med. 203:1999-2008. (Pubitemid 44188473)
77. Sasai M, Linehan MM, Iwasaki A. 2010. Bifurcation of Toll-like receptor 9 signaling by adaptor protein. Science 329:1530-34.
78. Weichhart T, SaemannMD. 2009. Themultiple facets ofmTORin immunity. Trends Immunol. 30:218-26.
79. Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, et al. 2008. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J. Exp. Med. 205:315-22. (Pubitemid 351281597)
80. Cao W, Manicassamy S, Tang H, Kasturi SP, Pirani A, et al. 2008. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTORp70S6K pathway. Nat. Immunol. 9:1157-64.
81. Tai LH, Goulet ML, Belanger S, Toyama-Sorimachi N, Fodil-Cornu N, et al. 2008. Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class IMHC. J. Exp.Med. 205:3187-99.
82. Yoshizaki M, Tazawa A, Kasumi E, Sasawatari S, Itoh K, et al. 2009. Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. Blood 114:1518-27.
83. Watarai H, Sekine E, Inoue S, Nakagawa R, Kaisho T, Taniguchi M. 2008. PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon. Proc. Natl. Acad. Sci. USA 105:2993-98. (Pubitemid 351723656)
84. Blasius AL, Colonna M. 2006. Sampling and signaling in plasmacytoid dendritic cells: the potential roles of Siglec-H. Trends Immunol. 27:255-60. (Pubitemid 43850406)
85. Martinelli E, Cicala C, Van Ryk D, Goode DJ, Macleod K, et al. 2007. HIV-1 gp120 inhibits TLR9-mediated activation and IFN-αsecretion in plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 104:3396-401. (Pubitemid 46364170)
86. Xu Y, Hu Y, Shi B, Zhang X, Wang J, et al. 2009. HBsAg inhibits TLR9-mediated activation and IFN-αproduction in plasmacytoid dendritic cells. Mol. Immunol. 46:2640-46.
87. O'Keeffe M, Grumont RJ, Hochrein H, Fuchsberger M, Gugasyan R, et al. 2005. Distinct roles for the NF-κB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals. Blood 106:3457-64. (Pubitemid 41609181)
88. Mouries J, Moron G, Schlecht G, Escriou N, Dadaglio G, Leclerc C. 2008. Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation. Blood 112:3713-22.
89. Young LJ, Wilson NS, Schnorrer P, Proietto A, ten Broeke T, et al. 2008. Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat. Immunol. 9:1244-52.
90. Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, et al. 2008. Direct proteasomeindependent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat. Immunol. 9:551-57. (Pubitemid 351560524)
91. Sadaka C, Marloie-Provost MA, Soumelis V, Benaroch P. 2009. Developmental regulation of MHC II expression and transport in human plasmacytoid-derived dendritic cells. Blood 113:2127-35.
92. Soumelis V, Liu YJ. 2006. From plasmacytoid to dendritic cell: morphological and functional switches during plasmacytoid pre-dendritic cell differentiation. Eur. J. Immunol. 36:2286-92. (Pubitemid 44420583)
93. Lindstedt M, Lundberg K, BorrebaeckCA. 2005. Gene family clustering identifies functionally associated subsets of human in vivo blood and tonsillar dendritic cells. J. Immunol. 175:4839-46. (Pubitemid 41456365)
94. Zuniga EI, McGavern DB, Pruneda-Paz JL, Teng C, Oldstone MB. 2004. Bone marrow plasmacytoid dendritic cells can differentiate intomyeloid dendritic cells upon virus infection. Nat. Immunol. 5:1227-34. (Pubitemid 41057737)
95. Liou LY, Blasius AL, Welch MJ, Colonna M, Oldstone MB, Zuniga EI. 2008. In vivo conversion of BM plasmacytoid DC into CD11b+ conventional DC during virus infection. Eur. J. Immunol. 38:3388-94.
96. Kool M, van Nimwegen M, WillartMA, Muskens F, Boon L, et al. 2009. An anti-inflammatory role for plasmacytoid dendritic cells in allergic airway inflammation. J. Immunol. 183:1074-82.
97. Liu C, Lou Y, Lizee G, Qin H, Liu S, et al. 2008. Plasmacytoid dendritic cells induceNKcell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J. Clin. Investig. 118:1165-75. (Pubitemid 351364623)
98. Pepper M, Dzierszinski F, Wilson E, Tait E, Fang Q, et al. 2008. Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines. J. Immunol. 180:6229-36.
99. Ang DK, Oates CV, Schuelein R, Kelly M, Sansom FM, et al. 2010. Cutting edge: pulmonary Legionella pneumophila is controlled by plasmacytoid dendritic cells but not type I IFN. J. Immunol. 184:5429-33.
100. Sapoznikov A, Fischer JA, Zaft T, Krauthgamer R, Dzionek A, Jung S. 2007. Organ-dependent in vivo priming of naive CD4+, but notCD8+, Tcells by plasmacytoid dendritic cells. J. Exp.Med. 204:1923-33. (Pubitemid 47236327)
101. Cella M, Facchetti F, Lanzavecchia A, Colonna M. 2000. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nat. Immunol. 1:305-10.
102. Boonstra A, Asselin-Paturel C, Gilliet M, Crain C, Trinchieri G, et al. 2003. Flexibility ofmouse classical and plasmacytoid-derived dendritic cells in directingThelper type 1 and 2 cell development: dependency on antigen dose and differential Toll-like receptor ligation. J. Exp. Med. 197:101-9. (Pubitemid 36110261)
103. Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V. 2004. CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens. J. Exp. Med. 199:567-79. (Pubitemid 38233840)
104. Hoeffel G, Ripoche AC, Matheoud D, Nascimbeni M, Escriou N, et al. 2007. Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity 27:481-92. (Pubitemid 47418679)
105. Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, et al. 2004. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells. J. Immunol. 173:4433-42. (Pubitemid 39280673)
106. Ito T, Yang M, Wang YH, Lande R, Gregorio J, et al. 2007. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204:105-15. (Pubitemid 46148761)
107. Martin-Gayo E, Sierra-Filardi E, Corbi AL, ToribioML. 2010. Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development. Blood 115:5366-75.
108. Sharma MD, Baban B, Chandler P, Hou DY, Singh N, et al. 2007. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J. Clin. Investig. 117:2570-82. (Pubitemid 47494358)
109. Ochando JC, Homma C, Yang Y, Hidalgo A, Garin A, et al. 2006. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat. Immunol. 7:652-62. (Pubitemid 43797347)
110. Irla M, K̈upfer N, Suter T, Lissilaa R, Benkhoucha M, et al. 2010.MHCclass II-restricted antigen presentation by plasmacytoid dendritic cells inhibitsTcell-mediated autoimmunity. J. Exp.Med. 207:1891-905.
111. Hadeiba H, Sato T, Habtezion A, Oderup C, Pan J, Butcher EC. 2008. CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease. Nat. Immunol. 9:1253-60.
112. Johnson BA 3rd, Kahler DJ, Baban B, Chandler PR, Kang B, et al. 2010. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2, 3-dioxygenase. Proc. Natl. Acad. Sci. USA 107:10644-48.
113. Koyama M, Hashimoto D, Aoyama K, Matsuoka K, Karube K, et al. 2009. Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells. Blood 113:2088-95.
114. Goubier A, Dubois B, Gheit H, Joubert G, Villard-Truc F, et al. 2008. Plasmacytoid dendritic cells mediate oral tolerance. Immunity 29:464-75.
115. Albert ML, Decalf J, Pol S. 2008. Plasmacytoid dendritic cells move down on the list of suspects: in search of the immune pathogenesis of chronic hepatitis C. J. Hepatol. 49:1069-78.
116. Takahashi K, Asabe S, Wieland S, Garaigorta U, Gastaminza P, et al. 2010. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc. Natl. Acad. Sci. USA 107:7431-36.
117. Yonkers NL, Rodriguez B, Milkovich KA, Asaad R, Lederman MM, et al. 2007. TLR ligand-dependent activation of naive CD4 T cells by plasmacytoid dendritic cells is impaired in hepatitis C virus infection. J. Immunol. 178:4436-44. (Pubitemid 46492395)
118. Decalf J, Fernandes S, Longman R, Ahloulay M, Audat F, et al. 2007. Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronicHCV patients. J. Exp. Med. 204:2423-37. (Pubitemid 47529327)
119. Fitzgerald-Bocarsly P, Jacobs ES. 2010. Plasmacytoid dendritic cells in HIV infection: striking a delicate balance. J. Leukoc. Biol. 87:609-20.
120. Meier A, Chang JJ, Chan ES, Pollard RB, SidhuHK, et al. 2009. Sex differences in theToll-like receptormediated response of plasmacytoid dendritic cells to HIV-1. Nat. Med. 15:955-59.
121. Mandl JN, Barry AP, Vanderford TH, Kozyr N, Chavan R, et al. 2008. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat. Med. 14:1077-87.
122. Wolf AI, Buehler D, Hensley SE, Cavanagh LL, Wherry EJ, et al. 2009. Plasmacytoid dendritic cells are dispensable during primary influenza virus infection. J. Immunol. 182:871-79.
123. Jung A, Kato H, Kumagai Y, Kumar H, Kawai T, et al. 2008. Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response viaMyD88. J. Virol. 82:196-206. (Pubitemid 350309136)
124. Dalod M, Salazar-Mather TP, Malmgaard L, Lewis C, Asselin-Paturel C, et al. 2002. Interferon α/βand interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. J. Exp. Med. 195:517-28. (Pubitemid 34461304)
125. Wang H, Peters N, Schwarze J. 2006. Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection. J. Immunol. 177:6263-70. (Pubitemid 44628844)
126. Smit JJ, Rudd BD, Lukacs NW. 2006. Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J. Exp. Med. 203:1153-59. (Pubitemid 43736586)
127. Lund JM, Linehan MM, Iijima N, Iwasaki A. 2006. Cutting edge: plasmacytoid dendritic cells provide innate immune protection against mucosal viral infection in situ. J. Immunol. 177:7510-14. (Pubitemid 44846264)
128. Cervantes-Barragan L, Zust R, Weber F, Spiegel M, Lang KS, et al. 2007. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood 109:1131-37. (Pubitemid 46220660)
129. Bocharov G, Zust R, Cervantes-Barragan L, Luzyanina T, Chiglintsev E, et al. 2010. A systems immunology approach to plasmacytoid dendritic cell function in cytopathic virus infections. PLoS Pathog. 6:e1001017.
130. Zuniga EI, Liou LY, Mack L, Mendoza M, Oldstone MB. 2008. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe 4:374-86.
131. Lee LN, Burke S, Montoya M, Borrow P. 2009. Multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice. J. Immunol. 182:7178-89.
132. Ronnblom L, Alm GV. 2001. A pivotal role for the natural interferon α-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J. Exp. Med. 194:F59-63. (Pubitemid 34028649)
133. Ronnblom L, Alm GV, ElorantaML. 2009. Type I interferon and lupus. Curr. Opin. Rheumatol. 21:471-77.
134. Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, et al. 2005. Plasmacytoid predendritic cells initiate psoriasis through interferon- αproduction. J. Exp. Med. 202:135-43. (Pubitemid 41002916)
135. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, et al. 2007. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449:564-69. (Pubitemid 47525141)
136. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, et al. 2009. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 206:1983-94.
137. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. 2001. Plasmacytoid dendritic cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am. J. Pathol. 159:237-43. (Pubitemid 33704208)
138. Bave U, Magnusson M, Eloranta ML, Perers A, Alm GV, Ronnblom L. 2003. FcγRIIa is expressed on natural IFN-α-producing cells (plasmacytoid dendritic cells) and is required for the IFN-αproduction induced by apoptotic cells combined with lupus IgG. J. Immunol. 171:3296-302. (Pubitemid 37093557)
139. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, et al. 2005. Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202:1131-39. (Pubitemid 41464506)
140. Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD. 2005. Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J. Clin. Investig. 115:407-17. (Pubitemid 40385482)
141. Tian J, Avalos AM, Mao SY, Chen B, Senthil K, et al. 2007. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat. Immunol. 8:487-96. (Pubitemid 46605917)
142. Lepelletier Y, Zollinger R, Ghirelli C, Raynaud F, Hadj-Slimane R, et al. 2010. Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid pre-dendritic cells (pDC). Blood 107:15181-86.
143. Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D, et al. 2010. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465:937-41.
144. Bave U, Nordmark G, Lovgren T, Ronnelid J, Cajander S, et al. 2005. Activation of the type I interferon system in primary Sjogren's syndrome: a possible etiopathogenic mechanism. Arthritis Rheum. 52:1185-95. (Pubitemid 40530126)
145. Isaksson M, Ardesjo B, Ronnblom L, Kampe O, Lassmann H, et al. 2009. Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE. Eur. J. Immunol. 39:2925-35.
146. Bailey-Bucktrout SL, Caulkins SC, Goings G, Fischer JA, Dzionek A, Miller SD. 2008. Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J. Immunol. 180:6457-61.
147. Saxena V, Ondr JK, Magnusen AF, Munn DH, Katz JD. 2007. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse. J. Immunol. 179:5041-53.
148. Tisch R, Wang B. 2009. Role of plasmacytoid dendritic cells in type 1 diabetes: friend or foe? Diabetes 58:12-13.
149. Shlomchik MJ. 2009. Activating systemic autoimmunity: B's, T's, and tolls. Curr. Opin. Immunol. 21:626-33.
150. Kwissa M, Amara RR, Robinson HL, Moss B, Alkan S, et al. 2007. Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus. J. Exp. Med. 204:2733-46. (Pubitemid 350044795)
151. Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, et al. 2009. Neutralization of interferon-α/β-inducible genes and downstream effect in a phase I trial of an anti-interferon-αmonoclonal antibody in systemic lupus erythematosus. Arthritis Rheum. 60:1785-96.
152. Barrat FJ, Meeker T, Chan JH, Guiducci C, Coffman RL. 2007. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur. J. Immunol. 37:3582-86