A hitchhiker's guide to myeloid cell subsets: Practical implementation of a novel mononuclear phagocyte classification system

Frontiers in Immunology

Volumn 6, Issue JUL, 2015, Pages

  Guilliams, Martin ^a,b   van de Laar, Lianne ^a,b  

^a GHENT UNIVERSITY   (Belgium)

^b GHENT UNIVERSITY HOSPITAL   (Belgium)

Author keywords

Classification; Dendritic Cells; Macrophages; Monocytes; Nomenclature

Indexed keywords

CD103 ANTIGEN; CD11B ANTIGEN; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 4; TUMOR NECROSIS FACTOR RECEPTOR;

ARTICLE; BONE MARROW CELL; CELIAC DISEASE; CELL METABOLISM; DENDRITIC CELL; FOOD ALLERGY; GENE EXPRESSION; HEMATOPOIESIS; HUMAN; IMMUNOMODULATION; INFLAMMATORY BOWEL DISEASE; KUPFFER CELL; MACROPHAGE; MONONUCLEAR PHAGOCYTE; NONHUMAN; ONTOGENY; PHAGOCYTOSIS; POLARIZATION; SELECTIVE SWEEP; TRANSCRIPTOMICS; WOUND HEALING;

EID: 84938528519     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00406     Document Type: Article

References (124)

1. Adams, D. (1979). The hitch hiker's guide to the galaxy. London: Pan Books.
2. Ajami, B., Bennett, J.L., Krieger, C, Mcnagny, K.M., and Rossi, F.M. (2011). Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nature neuroscience 14, 1142-1149. doi: 10.1038/nn.2887.
3. Ajami, B., Bennett, J.L., Krieger, C, Tetzlaff, W., and Rossi, F.M. (2007). Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nature neuroscience 10, 1538-1543. doi: 10.1038/nn2014.
4. Bachem, A., Guttler, S., Hartung, E., Ebstein, F., Schaefer, M., Tannert, A., Salama, A., Movassaghi, K., Opitz, C, Mages, H.W., Henn, V., Kloetzel, P.M., Gurka, S., and Kroczek, R.A. (2010). Superior antigen cross-presentation and XCR1 expression define human CDllc+CD141+ cells as homologues of mouse CD8+ dendritic cells. The Journal of experimental medicine 207, 1273-1281. doi: 10.1084/jem.20100348.
5. Bachem, A., Hartung, E., Guttler, S., Mora, A., Zhou, X., Hegemann, A., Plantinga, M., Mazzini, E., Stoitzner, P., Gurka, S., Henn, V., Mages, H.W., and Kroczek, R.A. (2012). Expression of XCR1 Characterizes the Batf3-Dependent Lineage of Dendritic Cells Capable of Antigen Cross-Presentation. Frontiers in immunology 3, 214. doi: 10.3389/fimmu.2012.00214.
6. Bain, C.C., Bravo-Blas, A., Scott, C.L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L.C., Artis, D., and Mowat, A.M. (2014). Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nature immunology 15, 929-937. doi: 10.1038/ni.2967.
7. Bain, C.C., Scott, C.L., Uronen-Hansson, H., Gudjonsson, S., Jansson, O., Grip, O., Guilliams, M., Malissen, B., Agace, W.W., and Mowat, A.M. (2012). Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors. Mucosal immunology, doi: 10.1038/mi.2012.89.
8. Balan, S., Ollion, V., Colletti, N., Chelbi, R., Montanana-Sanchis, F., Liu, H., Vu Manh, T.P., Sanchez, C, Savoret, J., Perrot, I., Doffin, A.C., Fossum, E., Bechlian, D., Chabannon, C, Bogen, B., Asselin-Paturel, C, Shaw, M., Soos, T., Caux, C, Valladeau-Guilemond, J., and Dalod, M. (2014). Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. Journal of immunology 193, 1622-1635. doi: 10.4049/jimmunol.1401243.
9. Becker, M., Guttler, S., Bachem, A., Hartung, E., Mora, A., Jakel, A., Hutloff, A., Henn, V., Mages, H.W., Gurka, S., and Kroczek, R.A. (2014). Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPalpha. Frontiers in immunology 5, 326. doi: 10.3389/fimmu.2014.00326.
10. Benson, M.J., Pino-Lagos, K., Rosemblatt, M., and Noelle, R.J. (2007). All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 204, 1765-1774.
11. 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., and Merad, M. (2009). Origin of the Lamina Propria Dendritic Cell Network. Immunity.
12. Breton, G., Lee, J., Zhou, Y.J., Schreiber, J.J., Keler, T., Puhr, S., Anandasabapathy, N., Schlesinger, S., Caskey, M., Liu, K., and Nussenzweig, M.C. (2015). Circulating precursors of human CD1c+ and CD 141+ dendritic cells. The Journal of experimental medicine 212, 401-413. doi: 10.1084/jem.20141441.
13. Caton, M.L., Smith-Raska, M.R., and Reizis, B. (2007). Notch-RBP-J signaling controls the homeostasis of CD8-dendritic cells in the spleen. J Exp Med 204, 1653-1664. doi: 10.1084/jem.20062648.
14. Caux, C., Vanbervliet, B., Massacrier, C., Dezutter-Dambuyant, C., De Saint-Vis, B., Jacquet, C., Yoneda, K., Imamura, S., Schmitt, D., and Banchereau, J. (1996). CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. The Journal of experimental medicine 184, 695-706.
15. Cheong, C., Matos, I., Choi, J.H., Dandamudi, D.B., Shrestha, E., Longhi, M.P., Jeffrey, K.L., Anthony, R.M., Kluger, C., Nchinda, G., Koh, H., Rodriguez, A., Idoyaga, J., Pack, M., Velinzon, K., Park, C.G., and Steinman, R.M. (2010). Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. Cell 143, 416-429. doi: 10.1016/j.cell.2010.09.039.
16. Chorro, L., Sarde, A., Li, M., Woollard, K.J., Chambon, P., Malissen, B., Kissenpfennig, A., Barbaroux, J.B., Groves, R., and Geissmann, F. (2009). Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med 206, 3089-3100.
17. Chou, D.B., Sworder, B., Bouladoux, N., Roy, C.N., Uchida, A.M., Grigg, M., Robey, P.G., and Belkaid, Y. (2012). Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection. Journal of leukocyte biology 92,123-131. doi: 10.1189/jlb.1011527.
18. 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., and Reizis, B. (2008). Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135, 37-48. doi: 10.1016/j.cell.2008.09.016.
19. Contreras, V., Urien, C., Guiton, R., Alexandre, Y., Vu Manh, T.P., Andrieu, T., Crozat, K., Jouneau, L., Bertho, N., Epardaud, M., Hope, J., Savina, A., Amigorena, S., Bonneau, M., Dalod, M., and Schwartz-Cornil, I. (2010). Existence of CD8alpha-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species. J Immunol 185, 3313-3325. doi: jimmunol.1000824 [pii] 10.4049/jimmunol.1000824.
20. Coombes, J.L., Siddiqui, K.R., Arancibia-Carcamo, C.V., Hall, J., Sun, C.M., Belkaid, Y., and Powrie, F. (2007). A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204,1757-1764.
21. Crozat, K., Guiton, R., Contreras, V., Feuillet, V., Dutertre, C.A., Ventre, E., Vu Manh, T.P., Baranek, T., Storset, A.K., Marvel, J., Boudinot, P., Hosmalin, A., Schwartz-Cornil, I., and Dalod, M. (2010a). The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J Exp Med 207, 1283-1292. doi: jem.20100223 [pii] 10.1084/jem.20100223.
22. Crozat, K., Guiton, R., Guilliams, M., Henri, S., Baranek, T., Schwartz-Cornil, I., Malissen, B., and Dalod, M. (2010b). Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol Rev 234,177-198. doi: IMR868 [pii] 10.1111/j.0105-2896.2009.00868.x.
23. Crozat, K., Tamoutounour, S., Vu Manh, T.P., Fossum, E., Luche, H., Ardouin, L., Guilliams, M., Azukizawa, H., Bogen, B., Malissen, B., Henri, S., and Dalod, M. (2011). Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and migratory dendritic cells of the CD8alpha+ type. Journal of immunology 187, 4411-4415. doi: 10.4049/jimmunol.1101717.
24. Desch, A.N., Gibbings, S.L., Clambey, E.T., Janssen, W.J., Slansky, J.E., Kedl, R.M., Henson, P.M., and Jakubzick, C. (2014). Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction. Nature communications 5, 4674. doi: 10.1038/ncomms5674.
25. Diao, J., Winter, E., Cantin, C., Chen, W., Xu, L., Kelvin, D., Phillips, J., and Cattral, M.S. (2006). In situ replication of immediate dendritic cell (DC) precursors contributes to conventional DC homeostasis in lymphoid tissue. J Immunol 176, 7196-7206.
26. Durand, M., and Segura, E. (2015). The known unknowns of the human dendritic cell network. Frontiers in immunology 6, 129. doi: 10.3389/fimmu.2015.00129.
27. 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., and Murphy, K.M. (2010). Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med207,823-836.
28. Epelman, S., Lavine, K.J., Beaudin, A.E., Sojka, D.K., Carrero, J.A., Calderon, B., Brija, T., Gautier, E.L., Ivanov, S., Satpathy, A.T., Schilling, J.D., Schwendener, R., Sergin, I., Razani, B., Forsberg, E.C., Yokoyama, W.M., Unanue, E.R., Colonna, M., Randolph, G.J., and Mann, D.L. (2014). Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40, 91-104. doi: 10.1016/j.immuni.2013.11.019.
29. Gao, Y., Nish, S.A., Jiang, R., Hou, L., Licona-Limon, P., Weinstein, J.S., Zhao, H., and Medzhitov, R. (2013). Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39, 722-732. doi: 10.1016/j.immuni.2013.08.028.
30. Gatto, D., Wood, K., Caminschi, I., Murphy-Durland, D., Schofield, P., Christ, D., Karupiah, G., and Brink, R. (2013). The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nature immunology 14, 446-453. doi: 10.1038/ni.2555.
31. Gautier, E.L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K.G., Gordonov, S., Mazloom, A.R., Maayan, A., Chua, W.J., Hansen, T.H., Turley, S.J., Merad, M., Randolph, G.J., and Immunological Genome, C. (2012). Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13,1118-1128. doi: 10.1038/ni.2419.
32. Geissmann, F., Jung, S., and Littman, D.R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71-82.
33. Geurtsvankessel, C.H., Bergen, I.M., Muskens, F., Boon, L., Hoogsteden, H.C., Osterhaus, A.D., Rimmelzwaan, G.F., and Lambrecht, B.N. (2009). Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection. PLoS One 4, e7187. doi: 10.1371/journal.pone.0007187.
34. Ghosh, H.S., Cisse, B., Bunin, A., Lewis, K.L., and Reizis, B. (2010). Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33, 905-916. doi: 10.1016/j.immuni.2010.11.023.
35. Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M.F., Conway, S.J., Ng, L.G., Stanley, E.R., Samokhvalov, I.M., and Merad, M. (2010). Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841-845. doi: science.1194637 [pii] 10.1126/science.1194637.
36. Ginhoux, F., and Jung, S. (2014). Monocytes and macrophages: developmental pathways and tissue homeostasis. Nature reviews. Immunology 14, 392-404. doi: 10.1038/nri3671.
37. Ginhoux, F., Liu, K., Helft, J., Bogunovic, M., Greter, M., Hashimoto, D., Price, J., Yin, N., Bromberg, J., Lira, S.A., Stanley, E.R., Nussenzweig, M., and Merad, M. (2009). The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med 206, 3115-3130.
38. Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., De Bruijn, M.F., Geissmann, F., and Rodewald, H.R. (2015). Tissue-resident macrophages originate from yolk-sac-derivederythro-myeloid progenitors. Nature 518, 547-551. doi: 10.1038/nature13989.
39. Grajales-Reyes, G.E., Iwata, A., Albring, J., Wu, X., Tussiwand, R., Kc, W., Kretzer, N.M., Briseno, C.G., Durai, V., Bagadia, P., Haldar, M., Schonheit, J., Rosenbauer, F., Murphy, T.L., and Murphy, K.M. (2015). Batf3 maintains autoactivation of Irf8 for commitment of a CD8alpha conventional DC clonogenic progenitor. Nature immunology. doi: 10.1038/ni.3197.
40. Guilliams, M., Crozat, K., Henri, S., Tamoutounour, S., Grenot, P., Devilard, E., De Bovis, B., Alexopoulou, L., Dalod, M., and Malissen, B. (2010a). Skin-draining lymph nodes contain dermis-derived CD103(-) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood 115,1958-1968.
41. Guilliams, M., De Kleer, I., Henri, S., Post, S., Vanhoutte, L., De Prijck, S., Deswarte, K., Malissen, B., Hammad, H., and Lambrecht, B.N. (2013). Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med 210, 1977-1992. doi: 10.1084/jem.20131199.
42. Guilliams, M., Ginhoux, F., Jakubzick, C., Naik, S.H., Onai, N., Schraml, B.U., Segura, E., Tussiwand, R., and Yona, S. (2014). Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nature reviews. Immunology 14, 571-578. doi: 10.1038/nri3712.
43. Guilliams, M., Henri, S., Tamoutounour, S., Ardouin, L., Schwartz-Cornil, I., Dalod, M., and Malissen, B. (2010b). From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets. Eur J Immunol 40, 2089-2094. doi: 10.1002/eji.201040498.
44. Guilliams, M., and Malissen, B. (2015). A Death Notice for In-Vitro-Generated GM-CSF Dendritic Cells? Immunity 42, 988-990. doi: 10.1016/j.immuni.2015.05.020.
45. Guilliams, M., Movahedi, K., Bosschaerts, T., Vandendriessche, T., Chuah, M.K., Herin, M., Acosta-Sanchez, A., Ma, L., Moser, M., Van Ginderachter, J.A., Brys, L., De Baetselier, P., and Beschin, A. (2009). IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection. J Immunol 182,1107-1118.
46. Gurka, S., Hartung, E., Becker, M., and Kroczek, R.A. (2015). Mouse Conventional Dendritic Cells Can be Universally Classified Based on the Mutually Exclusive Expression of XCR1 and SIRPalpha. Frontiers in immunology 6, 35. doi: 10.3389/fimmu.2015.00035.
47. 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., and Zenke, M. (2003). Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol 4, 380-386. doi: 10.1038/ni903.
48. Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M.B., Leboeuf, M., Becker, C.D., See, P., Price, J., Lucas, D., Greter, M., Mortha, A., Boyer, S.W., Forsberg, E.C., Tanaka, M., Van Rooijen, N., Garcia-Sastre, A., Stanley, E.R., Ginhoux, F., Frenette, P.S., and Merad, M. (2013). Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38, 792-804. doi: 10.1016/j.immuni.2013.04.004.
49. Helft, J., Bottcher, J., Chakravarty, P., Zelenay, S., Huotari, J., Schraml, B.U., Goubau, D., and Reis, E.S.C. (2015). GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells. Immunity 42, 1197-1211. doi: 10.1016/j.immuni.2015.05.018.
50. Hettinger, J., Richards, D.M., Hansson, J., Barra, M.M., Joschko, A.C., Krijgsveld, J., and Feuerer, M. (2013). Origin of monocytes and macrophages in a committed progenitor. Nat Immunol 14, 821-830. doi: 10.1038/ni.2638.
51. 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., and Murphy, K.M. (2008). Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322, 1097-1100.
52. Hoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F.F., See, P., Beaudin, A.E., Lum, J., Low, I., Forsberg, E.C., Poidinger, M., Zolezzi, F., Larbi, A., Ng, L.G., Chan, J.K., Greter, M., Becher, B., Samokhvalov, I.M., Merad, M., and Ginhoux, F. (2015). C-myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42, 665-678. doi: 10.1016/j.immuni.2015.03.011.
53. Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., Choy, S.H., Grisotto, M., Renia, L., Conway, S.J., Stanley, E.R., Chan, J.K., Ng, L.G., Samokhvalov, I.M., Merad, M., and Ginhoux, F. (2012). Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. The Journal of experimental medicine. doi: 10.1084/jem.20120340.
54. Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S., and Steinman, R.M. (1992). Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. The Journal of experimental medicine 176,1693-1702.
55. 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, and Belz, G.T. (2011). Id2 expression delineates differential checkpoints in the genetic program of CD8alpha+ and CD103+ dendritic cell lineages. EMBO J30,2690-2704. doi: emboj2011163 [pii] 10.1038/emboj.2011.163.
56. Jaitin, D.A., Kenigsberg, E., Keren-Shaul, H., Elefant, N., Paul, F., Zaretsky, I., Mildner, A., Cohen, N., Jung, S., Tanay, A., and Amit, I. (2014). Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343, 776-779. doi: 10.1126/science.1247651.
57. Jakubzick, C., Gautier, E.L., Gibbings, S.L., Sojka, D.K., Schlitzer, A., Johnson, T.E., Ivanov, S., Duan, Q., Bala, S., Condon, T., Van Rooijen, N., Grainger, J.R., Belkaid, Y., Ma'ayan, A., Riches, D.W., Yokoyama, W.M., Ginhoux, F., Henson, P.M., and Randolph, G.J. (2013). Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39, 599-610. doi: 10.1016/j.immuni.2013.08.007.
58. Jang, M.H., Sougawa, N., Tanaka, T., Hirata, T., Hiroi, T., Tohya, K., Guo, Z., Umemoto, E., Ebisuno, Y., Yang, B.G., Seoh, J.Y., Lipp, M., Kiyono, H., and Miyasaka, M. (2006). CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes. Journal of immunology 176, 803-810.
59. Janssen, W.J., Barthel, L., Muldrow, A., Oberley-Deegan, R.E., Kearns, M.T., Jakubzick, C., and Henson, P.M. (2011). Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. American journal of respiratory and critical care medicine 184, 547-560. doi: 10.1164/rccm.201011-1891OC.
60. Jha, A.K., Huang, S.C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., Chmielewski, K., Stewart, K.M., Ashall, J., Everts, B., Pearce, E.J., Driggers, E.M., and Artyomov, M.N. (2015). Network Integration of Parallel Metabolic and Transcriptional Data Reveals Metabolic Modules that Regulate Macrophage Polarization. Immunity 42, 419-430. doi: 10.1016/j.immuni.2015.02.005.
61. Karsunky, H., Merad, M., Cozzio, A., Weissman, I.L., and 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. doi: 10.1084/jem.20030323jem.20030323 [pii].
62. Kashiwada, M., Pham, N.L., Pewe, L.L., Harty, J.T., and Rothman, P.B. (2011). NFIL3/E4BP4 is a key transcription factor for CD8alpha(+) dendritic cell development. Blood 117, 6193-6197. doi: 10.1182/blood-2010-07-295873.
63. Kuipers, H., Soullie, T., Hammad, H., Willart, M., Kool, M., Hijdra, D., Hoogsteden, H.C., and Lambrecht, B.N. (2009). Sensitization by intratracheally injected dendritic cells is independent of antigen presentation by host antigen-presenting cells. JLeukocBiol 85, 64-70. doi: jlb.0807519 [pii] 10.1189/jlb.0807519.
64. Lavin, Y., Winter, D., Blecher-Gonen, R., David, E., Keren-Shaul, H., Merad, M., Jung, S., and Amit, I. (2014). Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312-1326. doi: 10.1016/j.cell.2014.11.018.
65. Lee, J., Breton, G., Oliveira, T.Y., Zhou, Y.J., Aljoufi, A., Puhr, S., Cameron, M.J., Sekaly, R.P., Nussenzweig, M.C., and Liu, K. (2015). Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. The Journal of experimental medicine 212, 385-399. doi: 10.1084/jem.20141442.
66. Lewis, K.L., Caton, M.L., Bogunovic, M., Greter, M., Grajkowska, L.T., Ng, D., Klinakis, A., Charo, I.F., Jung, S., Gommerman, J.L., Ivanov, Ii, Liu, K., Merad, M., and Reizis, B. (2011). Notch2 receptor signaling controls functional differentiation of dendritic cells in the spleen and intestine. Immunity 35, 780-791. doi: 10.1016/j.immuni.2011.08.013.
67. 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., and 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
68. Merad, M., Sathe, P., Helft,J., Miller,J., and Mortha, A. (2013). The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annual review of immunology 31, 563-604. doi: 10.1146/annurev-immunol-020711-074950.
69. Miller, M.A., Feng, X.J., Li, G., and Rabitz, H.A. (2012). Identifying biological network structure, predicting network behavior, and classifying network state with High Dimensional Model Representation (HDMR). PloS one 7, e37664. doi: 10.1371/journal.pone.0037664.
70. Molawi, K., Wolf, Y., Kandalla, P.K., Favret, J., Hagemeyer, N., Frenzel, K., Pinto, A.R., Klapproth, K., Henri, S., Malissen, B., Rodewald, H.R., Rosenthal, N.A., Bajenoff, M., Prinz, M., Jung, S., and Sieweke, M.H. (2014). Progressive replacement of embryo-derived cardiac macrophages with age. The Journal of experimental medicine 211, 2151-2158. doi: 10.1084/jem.20140639.
71. Murray, P.J., Allen, J.E., Biswas, S.K., Fisher, E.A., Gilroy, D.W., Goerdt, S., Gordon, S., Hamilton, J.A., Ivashkiv, L.B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F.O., Mege, J.L., Mosser, D.M., Natoli, G., Saeij, J.P., Schultze, J.L., Shirey, K.A., Sica, A., Suttles, J., Udalova, I., Van Ginderachter, J.A., Vogel, S.N., and Wynn, T.A. (2014). Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14-20. doi: 10.1016/j.immuni.2014.06.008.
72. Naik, S.H., Metcalf, D., Van Nieuwenhuijze, A., Wicks, I., Wu, L., Okeeffe, M., and Shortman, K. (2006). Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7, 663-671.
73. Naik, S.H., Proietto, A.I., Wilson, N.S., Dakic, A., Schnorrer, P., Fuchsberger, M., Lahoud, M.H., Okeeffe, M., Shao, Q.X., Chen, W.F., Villadangos, J.A., Shortman, K., and 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. doi: 174/11/6592 [pii].
74. 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., and 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.
75. Ohl, L., Mohaupt, M., Czeloth, N., Hintzen, G., Kiafard, Z., Zwirner, J., Blankenstein, T., Henning, G., and Forster, R. (2004). CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21, 279-288.
76. Onai, N., Kurabayashi, K., Hosoi-Amaike, M., Toyama-Sorimachi, N., Matsushima, K., Inaba, K., and Ohteki, T. (2013). A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential. Immunity 38, 943-957. doi: 10.1016/j.immuni.2013.04.006.
77. Onai, N., Obata-Onai, A., Schmid, M.A., Ohteki, T., Jarrossay, D., and 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.
78. Palucka, K.A., Taquet, N., Sanchez-Chapuis, F., and Gluckman, J.C. (1998). Dendritic cells as the terminal stage of monocyte differentiation. Journal of immunology 160, 4587-4595.
79. Persson, E.K., Uronen-Hansson, H., Semmrich, M., Rivollier, A., Hagerbrand, K., Marsal, J., Gudjonsson, S., Hakansson, U., Reizis, B., Kotarsky, K., and Agace, W.W. (2013). IRF4 Transcription-Factor-Dependent CD103CD11b Dendritic Cells Drive Mucosal T Helper 17 Cell Differentiation. Immunity. doi: 10.1016/j.immuni.2013.03.009.
80. Plantinga, M., Guilliams, M., Vanheerswynghels, M., Deswarte, K., Branco-Madeira, F., Toussaint, W., Vanhoutte, L., Neyt, K., Killeen, N., Malissen, B., Hammad, H., and Lambrecht, B.N. (2013). Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38, 322-335. doi: 10.1016/j.immuni.2012.10.016.
81. Poltorak, M.P., and Schraml, B.U. (2015). Fate mapping of dendritic cells. Frontiers in immunology 6,199. doi: 10.3389/fimmu.2015.00199.
82. 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., and Reis E Sousa, C. (2010). Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J Exp Med 207, 1261-1271. doi: jem.20092618 [pii] 10.1084/jem.20092618.
83. Pulendran, B., Banchereau, J., Burkeholder, S., Kraus, E., Guinet, E., Chalouni, C., Caron, D., Maliszewski, C., Davoust, J., Fay, J., and Palucka, K. (2000). Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo. J Immunol 165, 566-572.
84. Randolph, G.J., Inaba, K., Robbiani, D.F., Steinman, R.M., and Muller, W.A. (1999). Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11, 753-761.
85. Reynolds, G., and Haniffa, M. (2015). Human and Mouse Mononuclear Phagocyte Networks: A Tale of Two Species? Frontiers in immunology 6, 330. doi: 10.3389/fimmu.2015.00330.
86. Robbins, S.H., Walzer, T., Dembele, D., Thibault, C., Defays, A., Bessou, G., Xu, H., Vivier, E., Sellars, M., Pierre, P., Sharp, F.R., Chan, S., Kastner, P., and Dalod, M. (2008). Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol 9, R17. doi: gb-2008-9-1-r17 [pii] 10.1186/gb-2008-9-1-r17.
87. Sallusto, F., and 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 alpha. The Journal of experimental medicine 179,1109-1118.
88. Salomon, B., Cohen, J.L., Masurier, C., and Klatzmann, D. (1998). Three populations of mouse lymph node dendritic cells with different origins and dynamics. J Immunol 160, 708-717.
89. Satpathy, A.T., Briseno, C.G., Lee, J.S., Ng, D., Manieri, N.A., Kc, W., Wu, X., Thomas, S.R., Lee, W.L., Turkoz, M., Mcdonald, K.G., Meredith, M.M., Song, C., Guidos, C.J., Newberry, R.D., Ouyang, W., Murphy, T.L., Stappenbeck, T.S., Gommerman, J.L., Nussenzweig, M.C., Colonna, M., Kopan, R., and Murphy, K.M. (2013). Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol 14, 937-948. doi: 10.1038/ni.2679.
90. Saunders, D., Lucas, K., Ismaili, J., Wu, L., Maraskovsky, E., Dunn, A., and Shortman, K. (1996). Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor. J Exp Med 184, 2185-2196.
91. Schiavoni, G., Mattei, F., Sestili, P., Borghi, P., Venditti, M., Morse, H.C., 3rd, Belardelli, F., and Gabriele, L. (2002). ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J Exp Med 196, 1415-1425.
92. Schlitzer, A., Mcgovern, N., Teo, P., Zelante, T., Atarashi, K., Low, D., Ho, A.W., See, P., Shin, A., Wasan, P.S., Hoeffel, G., Malleret, B., Heiseke, A., Chew, S., Jardine, L., Purvis, H.A., Hilkens, C.M., Tam, J., Poidinger, M., Stanley, E.R., Krug, A.B., Renia, L., Sivasankar, B., Ng, L.G., Collin, M., Ricciardi-Castagnoli, P., Honda, K., Haniffa, M., and Ginhoux, F. (2013). IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38, 970-983. doi:10.1016/j.immuni.2013.04.011.
93. Schlitzer, A., Sivakamasundari, V., Chen, J., Sumatoh, H.R., Schreuder, J., Lum, J., Malleret, B., Zhang, S., Larbi, A., Zolezzi, F., Renia, L., Poidinger, M., Naik, S., Newell, E.W., Robson, P., and Ginhoux, F. (2015). Identification of cDC1-and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nature immunology. doi: 10.1038/ni.3200.
94. Schraml, B.U., Van Blijswijk, J., Zelenay, S., Whitney, P.G., Filby, A., Acton, S.E., Rogers, N.C., Moncaut, N., Carvajal, J.J., and Reis E Sousa, C. (2013). Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. Cell 154, 843-858. doi: 10.1016/j.cell.2013.07.014.
95. Schulz, C., Gomez Perdiguero, E., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S.E., Pollard, J.W., Frampton, J., Liu, K.J., and Geissmann, F. (2012). A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86-90. doi: science.1219179 [pii] 10.1126/science.1219179.
96. Scott, C.L., Henri, S., and Guilliams, M. (2014). Mononuclear phagocytes of the intestine, the skin, and the lung. Immunological reviews 262, 9-24. doi: 10.1111/imr.12220.
97. Serbina, N.V., Salazar-Mather, T.P., Biron, C.A., Kuziel, W.A., and Pamer, E.G. (2003). TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19, 59-70.
98. Shalek, A.K., Satija, R., Adiconis, X., Gertner, R.S., Gaublomme, J.T., Raychowdhury, R., Schwartz, S., Yosef, N., Malboeuf, C., Lu, D., Trombetta, J.J., Gennert, D., Gnirke, A., Goren, A., Hacohen, N., Levin, J.Z., Park, H., and Regev, A. (2013). Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 498, 236-240. doi: 10.1038/nature12172.
99. Siddiqui, K.R., Laffont, S., and Powrie, F. (2010). E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis. Immunity 32, 557-567. doi: S1074-7613(10)00124-X [pii] 10.1016/j.immuni.2010.03.017.
100. Sun, C.M., Hall, J.A., Blank, R.B., Bouladoux, N., Oukka, M., Mora, J.R., and Belkaid, Y. (2007). Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204, 1775-1785.
101. Suzuki, S., Honma, K., Matsuyama, T., Suzuki, K., Toriyama, K., Akitoyo, I., Yamamoto, K., Suematsu, T., Nakamura, M., Yui, K., and Kumatori, A. (2004). Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha-dendritic cell development. Proc Natl Acad Sci USA 101, 8981-8986. doi: 10.1073/pnas.04021391010402139101 [pii].
102. Swirski, F.K., Nahrendorf, M., Etzrodt, M., Wildgruber, M., Cortez-Retamozo, V., Panizzi, P., Figueiredo, J.L., Kohler, R.H., Chudnovskiy, A., Waterman, P., Aikawa, E., Mempel, T.R., Libby, P., Weissleder, R., and Pittet, M.J. (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612-616. doi: 10.1126/science.1175202.
103. Tailor, P., Tamura, T., Morse, H.C., 3rd, and Ozato, K. (2008). The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111, 1942-1945. doi: 10.1182/blood-2007-07-100750.
104. Tamoutounour, S., Guilliams, M., Montanana Sanchis, F., Liu, H., Terhorst, D., Malosse, C., Pollet, E., Ardouin, L., Luche, H., Sanchez, C., Dalod, M., Malissen, B., and Henri, S. (2013). Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925-938. doi: 10.1016/j.immuni.2013.10.004.
105. Tamoutounour, S., Henri, S., Lelouard, H., De Bovis, B., De Haar, C., Van Der Woude, C.J., Woltman, A.M., Reyal, Y., Bonnet, D., Sichien, D., Bain, C.C., Mc, I.M.A., Reis, E.S.C., Poulin, L.F., Malissen, B., and Guilliams, M. (2012). CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. European journal of immunology. doi: 10.1002/eji.201242847.
106. Tamura, T., Tailor, P., Yamaoka, K., Kong, H.J., Tsujimura, H., O'shea, J.J., Singh, H., and Ozato, K. (2005). IFN regulatory factor-4 and-8 govern dendritic cell subset development and their functional diversity. J Immunol 174, 2573-2581. doi: 174/5/2573 [pii].
107. Tussiwand, R., Everts, B., Grajales-Reyes, G.E., Kretzer, N.M., Iwata, A., Bagaitkar, J., Wu, X., Wong, R., Anderson, D.A., Murphy, T.L., Pearce, E.J., and Murphy, K.M. (2015). Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses. Immunity 42, 916-928. doi: 10.1016/j.immuni.2015.04.017.
108. Van Furth, R. (1980). "Identification of Mononuclear Phagocytes: Overview and Definitions,". in Methods for Studying Mononuclear Phagocytes. (London: Academic Press), 243-252.
109. Van Furth, R., Cohn, Z.A., Hirsch, J.G., Humphrey, J.H., Spector, W.G., and Langevoort, H.L. (1972). [Mononuclear phagocytic system: new classification of macrophages, monocytes and of their cell line]. Bull World Health Organ 47, 651-658.
110. Varol, C., Landsman, L., Fogg, D.K., Greenshtein, L., Gildor, B., Margalit, R., Kalchenko, V., Geissmann, F., and Jung, S. (2007). Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204, 171-180.
111. Varol, C., Mildner, A., and Jung, S. (2015). Macrophages: development and tissue specialization. Annual review of immunology 33, 643-675. doi: 10.1146/annurev-immunol-032414-112220.
112. Varol, C., Vallon-Eberhard, A., Elinav, E., Aychek, T., Shapira, Y., Luche, H., Fehling, H.J., Hardt, W.D., Shakhar, G., and Jung, S. (2009). Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31, 502-512.
113. Vu Manh, T.P., Bertho, N., Hosmalin, A., Schwartz-Cornil, I., and Dalod, M. (2015a). Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions. Frontiers in immunology 6, 260. doi: 10.3389/fimmu.2015.00260.
114. Vu Manh, T.P., Elhmouzi-Younes, J., Urien, C., Ruscanu, S., Jouneau, L., Bourge, M., Moroldo, M., Foucras, G., Salmon, H., Marty, H., Quere, P., Bertho, N., Boudinot, P., Dalod, M., and Schwartz-Cornil, I. (2015b). Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics. Frontiers in immunology 6, 299. doi: 10.3389/fimmu.2015.00299.
115. Vu Manh, T.P., Marty, H., Sibille, P., Le Vern, Y., Kaspers, B., Dalod, M., Schwartz-Cornil, I., and Quere, P. (2014). Existence of Conventional Dendritic Cells in Gallus gallus Revealed by Comparative Gene Expression Profiling. J Immunol. doi: 10.4049/jimmunol.1303405.
116. Waskow, C., Liu, K., Darrasse-Jeze, G., Guermonprez, P., Ginhoux, F., Merad, M., Shengelia, T., Yao, K., and Nussenzweig, M. (2008). The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nature immunology 9, 676-683. doi: 10.1038/ni.1615.
117. Wimmers, F., Schreibelt, G., Skold, A.E., Figdor, C.G., and De Vries, I.J. (2014). Paradigm Shift in Dendritic Cell-Based Immunotherapy: From in vitro Generated Monocyte-Derived DCs to Naturally Circulating DC Subsets. Frontiers in immunology 5,165. doi: 10.3389/fimmu.2014.00165.
118. Wu, L., D'amico, A., Winkel, K.D., Suter, M., Lo, D., and Shortman, K. (1998). RelB is essential for the development of myeloid-related CD8alpha-dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 9, 839-847.
119. Xu, Y., Zhan, Y., Lew, A.M., Naik, S.H., and Kershaw, M.H. (2007). Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking. Journal of immunology 179, 7577-7584.
120. Xue, J., Schmidt, S.V., Sander, J., Draffehn, A., Krebs, W., Quester, I., De Nardo, D., Gohel, T.D., Emde, M., Schmidleithner, L., Ganesan, H., Nino-Castro, A., Mallmann, M.R., Labzin, L., Theis, H., Kraut, M., Beyer, M., Latz, E., Freeman, T.C., Ulas, T., and Schultze, J.L. (2014). Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40, 274-288. doi: 10.1016/j.immuni.2014.01.006.
121. Yamasaki, R., Lu, H., Butovsky, O., Ohno, N., Rietsch, A.M., Cialic, R., Wu, P.M., Doykan, C.E., Lin, J., Cotleur, A.C., Kidd, G., Zorlu, M.M., Sun, N., Hu, W., Liu, L., Lee, J.C., Taylor, S.E., Uehlein, L., Dixon, D., Gu, J., Floruta, C.M., Zhu, M., Charo, I.F., Weiner, H.L., and Ransohoff, R.M. (2014). Differential roles of microglia and monocytes in the inflamed central nervous system. The Journal of experimental medicine 211, 1533-1549. doi: 10.1084/jem.20132477.
122. Yona, S., and Gordon, S. (2015). FROM THE RETICULOENDOTHELIAL TO MONONUCLEAR PHAGOCYTE SYSTEM-THE UNACCOUNTED YEARS. Frontiers in Immunology 6. doi: 10.3389/fimmu.2015.00328.
123. Yona, S., Kim, K.W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., Hume, D.A., Perlman, H., Malissen, B., Zelzer, E., and Jung, S. (2013). Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis. Immunity 38, 79-91. doi: 10.1016/j.immuni.2012.12.001S1074-7613(12)00548-1 [pii].
124. Zigmond, E., Samia-Grinberg, S., Pasmanik-Chor, M., Brazowski, E., Shibolet, O., Halpern, Z., and Varol, C. (2014). Infiltrating Monocyte-Derived Macrophages and Resident Kupffer Cells Display Different Ontogeny and Functions in Acute Liver Injury. Journal of immunology. doi: 10.4049/jimmunol.1400574.