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Annual Review of Immunology

Volume 33, 2015

Macrophages: Development and Tissue Specialization

Abstract

Macrophages are myeloid immune cells that are strategically positioned throughout the body tissues, where they ingest and degrade dead cells, debris, and foreign material and orchestrate inflammatory processes. Here we review two major recent paradigm shifts in our understanding of tissue macrophage biology. The first is the realization that most tissue-resident macrophages are established prenatally and maintained through adulthood by longevity and self-renewal. Their generation and maintenance are thus independent from ongoing hematopoiesis, although the cells can be complemented by adult monocyte-derived macrophages. Second, aside from being immune sentinels, tissue macrophages form integral components of their host tissue. This entails their specialization in response to local environmental cues to contribute to the development and specific function of their tissue of residence. Factors that govern tissue macrophage specialization are emerging. Moreover, tissue specialization is reflected in discrete gene expression profiles of macrophages, as well as epigenetic signatures reporting actual and potential enhancer usage.

Keyword(s): macrophages, monocyte fates, tissue specialization
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2015-03-21
2024-04-18
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Literature Cited

  1. Cavaillon J-M. 1.  2011. The historical milestones in the understanding of leukocyte biology initiated by Elie Metchnikoff. Soc. Leukoc. Biol. 90:413–24 [Google Scholar]
  2. Medzhitov R. 2.  2010. Inflammation 2010: new adventures of an old flame. Cell 140:6771–76 [Google Scholar]
  3. Medzhitov R. 3.  2008. Origin and physiological roles of inflammation. Nature 454:7203428–35 [Google Scholar]
  4. Wynn TA, Chawla A, Pollard JW. 4.  2013. Macrophage biology in development, homeostasis and disease. Nature 496:7446445–55 [Google Scholar]
  5. Davies LC, Jenkins SJ, Allen JE, Taylor PR. 5.  2013. Tissue-resident macrophages. Nat. Immunol. 14:10986–95 [Google Scholar]
  6. Epelman S, Lavine KJ, Randolph GJ. 6.  2014. Origin and functions of tissue macrophages. Immunity 41:121–35 [Google Scholar]
  7. Stefater JA III, Ren S, Lang RA, Duffield JS. 7.  2011. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends Mol. Med. 17:12743–52 [Google Scholar]
  8. Jenkins SJ, Hume DA. 8.  2014. Homeostasis in the mononuclear phagocyte system. Trends Immunol. 35:8358–67 [Google Scholar]
  9. van Furth R, Cohn ZA. 9.  1968. The origin and kinetics of mononuclear phagocytes. J. Exp. Med. 128:3415–35 [Google Scholar]
  10. van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. 10.  1972. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 46:6845–52 [Google Scholar]
  11. Steinman RM, Cohn ZA. 11.  1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137:51142–62 [Google Scholar]
  12. Merad M, Sathe P, Helft J, Miller J, Mortha A. 12.  2013. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31:1563–604 [Google Scholar]
  13. Mildner A, Jung S. 13.  2014. Development and function of dendritic cell subsets. Immunity 40:5642–56 [Google Scholar]
  14. Ginhoux F, Jung S. 14.  2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14:6392–404 [Google Scholar]
  15. Palis J, Robertson S, Kennedy M, Wall C, Keller G. 15.  1999. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126:225073–84 [Google Scholar]
  16. Bertrand JY, Jalil A, Klaine M, Jung S, Cumano A, Godin I. 16.  2005. Three pathways to mature macrophages in the early mouse yolk sac. Blood 106:93004–11 [Google Scholar]
  17. Cumano A, Godin I. 17.  2007. Ontogeny of the hematopoietic system. Annu. Rev. Immunol. 25:1745–85 [Google Scholar]
  18. Orkin SH, Zon LI. 18.  2008. Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132:4631–44 [Google Scholar]
  19. Kumaravelu P, Hook L, Morrison AM, Ure J, Zhao S. 19.  et al. 2002. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development 129:214891–99 [Google Scholar]
  20. McGrath KE. 20.  2002. Circulation is established in a stepwise pattern in the mammalian embryo. Blood 101:51669–75 [Google Scholar]
  21. Lang RA, Bishop JM. 21.  1993. Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74:3453–62 [Google Scholar]
  22. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS. 22.  et al. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131:61164–78 [Google Scholar]
  23. Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q. 23.  et al. 2010. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116:5829–40 [Google Scholar]
  24. McKercher SR, Torbett BE, Anderson KL, Henkel GW, Vestal DJ. 24.  et al. 1996. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15:205647–58 [Google Scholar]
  25. Dai XM. 25.  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 99:1111–20 [Google Scholar]
  26. Hoeffel G, Wang Y, Greter M, See P, Teo P. 26.  et al. 2012. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages. J. Exp. Med. 209:61167–81 [Google Scholar]
  27. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N. 27.  et al. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:607786–90 [Google Scholar]
  28. Sumner R, Crawford A, Mucenski M, Frampton J. 28.  2000. Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas subsequent development is strictly dependent on the transcription factor. Oncogene 19:303335–42 [Google Scholar]
  29. Lieu YK, Reddy EP. 29.  2009. Conditional c-myb knockout in adult hematopoietic stem cells leads to loss of self-renewal due to impaired proliferation and accelerated differentiation. PNAS 106:5121689–94 [Google Scholar]
  30. Soza-Ried C, Hess I, Netuschil N, Schorpp M, Boehm T. 30.  2010. Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. PNAS 107:4017304–8 [Google Scholar]
  31. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW. 31.  et al. 2000. Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20:114106–14 [Google Scholar]
  32. Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P. 32.  et al. 2006. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311:575783–87 [Google Scholar]
  33. Hettinger J, Richards DM, Hansson J, Barra MM, Joschko A-C. 33.  et al. 2013. Origin of monocytes and macrophages in a committed progenitor. Nat. Immunol. 14:8821–30 [Google Scholar]
  34. Jung K, Ohlrich B, Mildner D, Egger E. 34.  1978. Apoenzymes of aspartate aminotransferase and alanine aminotransferase in the serum of healthy subjects. Z. Med. Lab. Diagn. 19:3146–51 [Google Scholar]
  35. Yona S, Kim K-W, Wolf Y, Mildner A, Varol D. 35.  et al. 2012. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38:179–91 [Google Scholar]
  36. Alliot F, Godin I, Pessac B. 36.  1999. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Dev. Brain Res. 117:2145–52 [Google Scholar]
  37. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P. 37.  et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:6005841–45 [Google Scholar]
  38. Samokhvalov IM, Samokhvalova NI, Nishikawa S-I. 38.  2007. Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 446:71391056–61 [Google Scholar]
  39. Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA. 39.  et al. 2014. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:191–104 [Google Scholar]
  40. Guilliams M, De Kleer I, Henri S, Post S, Vanhoutte L. 40.  et al. 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. 210:101977–92 [Google Scholar]
  41. Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB. 41.  et al. 2013. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38:4792–804 [Google Scholar]
  42. Ginhoux F, Lim S, Hoeffel G, Low D, Huber T. 42.  2013. Origin and differentiation of microglia. Front. Cell. Neurosci. 7:45 [Google Scholar]
  43. Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C. 43.  et al. 2013. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16:273–80 [Google Scholar]
  44. Gomez Perdiguero E, Geissmann F. 44.  2013. Myb-independent macrophages: a family of cells that develops with their tissue of residence and is involved in its homeostasis. Cold Spring Harb. Symp. Quant. Biol. 78:91–100 [Google Scholar]
  45. Seré K, Baek J-H, Ober-Blöbaum J, Müller-Newen G, Tacke F. 45.  et al. 2012. Two distinct types of Langerhans cells populate the skin during steady state and inflammation. Immunity 37:5905–16 [Google Scholar]
  46. Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FMV. 46.  2011. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14:91142–49 [Google Scholar]
  47. Mildner A, Yona S, Jung S. 47.  2013. A close encounter of the third kind: monocyte-derived cells. Adv. Immunol. 120:69–103 [Google Scholar]
  48. Segura E, Amigorena S. 48.  2013. Inflammatory dendritic cells in mice and humans. Trends Immunol. 34:9440–45 [Google Scholar]
  49. Avraham-Davidi I, Yona S, Grunewald M, Landsman L, Cochain C. 49.  et al. 2013. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J. Exp. Med. 210:122611–25 [Google Scholar]
  50. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A. 50.  et al. 2013. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39:3599–610 [Google Scholar]
  51. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N. 51.  et al. 2014. Dendritic cells, monocytes and macrophages: a proposal for a unifying nomenclature based on ontogeny. Nat. Rev. Immunol. 14:571–78 [Google Scholar]
  52. Priller J, Flügel A, Wehner T, Boentert M, Haas CA. 52.  et al. 2001. Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment. Nat. Med. 7:121356–61 [Google Scholar]
  53. Kierdorf K, Katzmarski N, Haas CA, Prinz M. 53.  2013. Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias. PLOS ONE 8:3e58544 [Google Scholar]
  54. Serbina NV, Pamer EG. 54.  2006. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7:3311–17 [Google Scholar]
  55. Tamoutounour S, Henri S, Lelouard H, de Bovis B, de Haar C. 55.  et al. 2012. CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. Eur. J. Immunol. 42:3150–66 [Google Scholar]
  56. Mizutani M, Pino PA, Saederup N, Charo IF, Ransohoff RM, Cardona AE. 56.  2012. The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J. Immunol. 188:129–36 [Google Scholar]
  57. Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM. 57.  et al. 2014. Differential roles of microglia and monocytes in the inflamed central nervous system. J. Exp. Med. 10:121538–43 [Google Scholar]
  58. Goldmann T, Wieghofer P, Müller PF, Wolf Y, Varol D. 58.  et al. 2013. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat. Neurosci. 16:111618–26 [Google Scholar]
  59. Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B. 59.  et al. 2007. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J. Exp. Med. 204:1171–80 [Google Scholar]
  60. Cros J, Cagnard N, Woollard K, Patey N, Zhang S-Y. 60.  et al. 2010. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–86 [Google Scholar]
  61. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M. 61.  et al. 2010. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115:3e10–19 [Google Scholar]
  62. Mildner A, Chapnik E, Manor O, Yona S, Kim KW. 62.  et al. 2013. Mononuclear phagocyte microRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis. Blood 121:61016–27 [Google Scholar]
  63. Williams MJ. 63.  2007. Drosophila hemopoiesis and cellular immunity. J. Immunol. 178:84711–16 [Google Scholar]
  64. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V. 64.  et al. 2009. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:5940612–16 [Google Scholar]
  65. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM. 65.  et al. 2009. In vivo analysis of dendritic cell development and homeostasis. Science 324:5925392–97 [Google Scholar]
  66. Passlick B, Flieger D, Ziegler-Heitbrock HW. 66.  1989. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74:72527–34 [Google Scholar]
  67. Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM. 67.  et al. 2011. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes. Nat. Immunol. 12:8778–85 [Google Scholar]
  68. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O. 68.  et al. 2007. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:5838666–70 [Google Scholar]
  69. Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L. 69.  et al. 2013. Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153:2362–75 [Google Scholar]
  70. Noy R, Pollard JW. 70.  2014. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:149–61 [Google Scholar]
  71. McNelis JC, Olefsky JM. 71.  2014. Macrophages, immunity, and metabolic disease. Immunity 41:136–48 [Google Scholar]
  72. Chawla A, Nguyen KD, Goh YPS. 72.  2011. Macrophage-mediated inflammation in metabolic disease. Nat. Rev. Immunol. 11:11738–49 [Google Scholar]
  73. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B. 73.  et al. 2004. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:4409–21 [Google Scholar]
  74. Lin EY, Pollard JW. 74.  2007. Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Res. 67:115064–66 [Google Scholar]
  75. Laoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J. 75.  et al. 2014. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res. 74:124–30 [Google Scholar]
  76. Movahedi K, Laoui D, Gysemans C, Baeten M, Stangé G. 76.  et al. 2010. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 70:145728–39 [Google Scholar]
  77. Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR. 77.  et al. 2014. The cellular and molecular origin of tumor-associated macrophages. Science 344:6186921–25 [Google Scholar]
  78. Escobar G, Moi D, Ranghetti A, Ozkal-Baydin P, Squadrito ML. 78.  et al. 2014. Genetic engineering of hematopoiesis for targeted IFN-α delivery inhibits breast cancer progression. Sci. Transl. Med. 6:217217ra3 [Google Scholar]
  79. Van Nguyen A, Pollard JW. 79.  2002. Colony stimulating factor-1 is required to recruit macrophages into the mammary gland to facilitate mammary ductal outgrowth. Dev. Biol. 247:111–25 [Google Scholar]
  80. Moore KJ, Sheedy FJ, Fisher EA. 80.  2013. Macrophages in atherosclerosis: a dynamic balance. Nat. Rev. Immunol. 13:10709–21 [Google Scholar]
  81. Boring L, Gosling J, Chensue SW, Kunkel SL, Farese RV Jr. 81.  1997. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J. Clin. Investig. 100:102552–61 [Google Scholar]
  82. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R. 82.  et al. 2009. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113:4963–72 [Google Scholar]
  83. Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y. 83.  et al. 2013. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19:91166–72 [Google Scholar]
  84. Mildner A, Mack M, Schmidt H, Brück W, Djukic M. 84.  et al. 2009. CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132:92487–500 [Google Scholar]
  85. Vainchtein ID, Vinet J, Brouwer N, Brendecke S, Biagini G. 85.  et al. 2014. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia 62:101724–35 [Google Scholar]
  86. Weber B, Saurer L, Schenk M, Dickgreber N, Mueller C. 86.  2011. CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. Eur. J. Immunol. 41:3773–79 [Google Scholar]
  87. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT. 87.  et al. 2012. Ly6Chi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37:61076–90 [Google Scholar]
  88. Zigmond E, Samia-Grinberg S, Pasmanik-Chor M, Brazowski E, Shibolet O. 88.  et al. 2014. Infiltrating monocyte-derived macrophages and resident Kupffer cells display different ontogeny and functions in acute liver injury. J. Immunol. 193:1344–53 [Google Scholar]
  89. Shechter R, London A, Varol C, Raposo C, Cusimano M. 89.  et al. 2009. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLOS Med. 6:7e1000113 [Google Scholar]
  90. Chazaud B. 90.  2014. Macrophages: supportive cells for tissue repair and regeneration. Immunobiology 219:3172–78 [Google Scholar]
  91. Ramachandran P, Pellicoro A, Vernon MA, Boulter L, Aucott RL. 91.  et al. 2012. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. PNAS 109:E3186–95 [Google Scholar]
  92. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T. 92.  et al. 2007. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204:123037–47 [Google Scholar]
  93. Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N. 93.  et al. 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med. 204:51057–69 [Google Scholar]
  94. London A, Itskovich E, Benhar I, Kalchenko V, Mack M. 94.  et al. 2011. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med. 208:123–39 [Google Scholar]
  95. Crane MJ, Daley JM, van Houtte O, Brancato SK, Henry WL, Albina JE. 95.  2014. The monocyte to macrophage transition in the murine sterile wound. PLOS ONE 9:1e86660 [Google Scholar]
  96. Niess JH, Brand S, Gu X, Landsman L, Jung S. 96.  et al. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:5707254–58 [Google Scholar]
  97. Bain CC, Scott CL, Uronen-Hansson H, Gudjonsson S, Jansson O. 97.  et al. 2012. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol. 6:498–510 [Google Scholar]
  98. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y. 98.  et al. 2009. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31:3502–12 [Google Scholar]
  99. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D. 99.  et al. 2009. Origin of the lamina propria dendritic cell network. Immunity 31:3513–25 [Google Scholar]
  100. Jaensson E, Uronen-Hansson H, Pabst O, Eksteen B, Tian J. 100.  et al. 2008. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205:92139–49 [Google Scholar]
  101. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. 101.  2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118:2229–41 [Google Scholar]
  102. Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP. 102.  et al. 2014. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:61781249288 [Google Scholar]
  103. Seno H, Miyoshi H, Brown SL, Geske MJ, Colonna M, Stappenbeck TS. 103.  2009. Efficient colonic mucosal wound repair requires Trem2 signaling. PNAS 106:1256–61 [Google Scholar]
  104. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. 104.  2012. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J. Exp. Med. 209:1139–55 [Google Scholar]
  105. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L. 105.  et al. 2008. Regulatory T cell–derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:4546–58 [Google Scholar]
  106. Zigmond E, Bernshtein B, Friedlander G, Walker CR, Yona S. 106.  et al. 2014. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40:720–33 [Google Scholar]
  107. Bogunovic M, Mortha A, Muller PA, Merad M. 107.  2012. Mononuclear phagocyte diversity in the intestine. Immunol. Res. 54:1–337–49 [Google Scholar]
  108. Muller PA, Koscsó B, Rajani GM, Stevanovic K, Berres M-L. 108.  et al. 2014. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158:2300–13 [Google Scholar]
  109. Bain CC, Bravo-Blas A, Scott CL, Gomez Perdiguero E, Geissmann F. 109.  et al. 2014. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15:10929–37 [Google Scholar]
  110. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D. 110.  et al. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:5925–38 [Google Scholar]
  111. Malissen B, Tamoutounour S, Henri S. 111.  2014. The origins and functions of dendritic cells and macrophages in the skin. Nat. Rev. Immunol. 14:417–28 [Google Scholar]
  112. Molawi K, Wolf Y, Kandalla PK, Favret J, Hagemeyer N. 112.  et al. 2014. Gradual replacement of embryo-derived cardiac macrophages with age. J. Exp. Med. 211:112151–58 [Google Scholar]
  113. Tagliani E, Shi C, Nancy P, Tay C-S, Pamer EG, Erlebacher A. 113.  2011. Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1. J. Exp. Med. 208:91901–16 [Google Scholar]
  114. Hashimoto K, Joshi SK, Koni PA. 114.  2002. A conditional null allele of the major histocompatibility IA-beta chain gene. Genesis 32:2152–53 [Google Scholar]
  115. Alliot F, Lecain E, Grima B, Pessac B. 115.  1991. Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. PNAS 88:41541–45 [Google Scholar]
  116. Aziz A, Soucie E, Sarrazin S, Sieweke MH. 116.  2009. MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science 326:5954867–71 [Google Scholar]
  117. Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD. 117.  et al. 2011. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332:60351284–88 [Google Scholar]
  118. Ghigo C, Mondor I, Jorquera A, Nowak J, Wienert S. 118.  et al. 2013. Multicolor fate mapping of Langerhans cell homeostasis. J. Exp. Med. 210:91657–64 [Google Scholar]
  119. Barth MW, Hendrzak JA, Melnicoff MJ, Morahan PS. 119.  1995. Review of the macrophage disappearance reaction. J. Leukoc. Biol. 57:3361–67 [Google Scholar]
  120. Davies LC, Rosas M, Smith PJ, Fraser DJ, Jones SA, Taylor PR. 120.  2011. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur. J. Immunol. 41:82155–64 [Google Scholar]
  121. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR III. 121.  et al. 2013. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:71596–609 [Google Scholar]
  122. Rosas M, Davies LC, Giles PJ, Liao CT, Kharfan B. 122.  et al. 2014. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344:645–48 [Google Scholar]
  123. Gautier EL, Ivanov S, Williams JW, Huang SCC, Marcelin G. 123.  et al. 2014. Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. J. Exp. Med. 211:81525–31 [Google Scholar]
  124. Jenkins SJ, Ruckerl D, Thomas GD, Hewitson JP, Duncan S. 124.  et al. 2013. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J. Exp. Med. 210:112477–91 [Google Scholar]
  125. Sieweke MH, Allen JE. 125.  2013. Beyond stem cells: self-renewal of differentiated macrophages. Science 342:61611242974 [Google Scholar]
  126. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y. 126.  et al. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8:6752–58 [Google Scholar]
  127. Nimmerjahn A. 127.  2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:57261314–18 [Google Scholar]
  128. Stuart LM, Ezekowitz RAB. 128.  2005. Phagocytosis: elegant complexity. Immunity 22:5539–50 [Google Scholar]
  129. Bogdan C, Vodovotz Y, Nathan C. 129.  1991. Macrophage deactivation by interleukin 10. J. Exp. Med. 174:61549–55 [Google Scholar]
  130. Gordon S. 130.  2003. Alternative activation of macrophages. Nat. Rev. Immunol. 3:123–35 [Google Scholar]
  131. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ. 131.  et al. 2014. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci. 17:1131–43 [Google Scholar]
  132. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM. 132.  et al. 2006. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9:7917–24 [Google Scholar]
  133. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R. 133.  et al. 2000. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:54971768–71 [Google Scholar]
  134. Snelgrove RJ, Goulding J, Didierlaurent AM, Lyonga D, Vekaria S. 134.  et al. 2008. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat. Immunol. 9:91074–83 [Google Scholar]
  135. Gautier EL, Shay T, Miller J, Greter M, Jakubzick C. 135.  et al. 2012. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13:1118–28 [Google Scholar]
  136. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H. 136.  et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:61312–26 [Google Scholar]
  137. Beck JM, Young VB, Huffnagle GB. 137.  2012. The microbiome of the lung. Transl. Res. 160:4258–66 [Google Scholar]
  138. Guilliams M, Lambrecht BN, Hammad H. 138.  2013. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 6:3464–73 [Google Scholar]
  139. Gollwitzer ES, Saglani S, Trompette A, Yadava K, Sherburn R. 139.  et al. 2014. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20:6642–47 [Google Scholar]
  140. Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD. 140.  et al. 2003. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 422:6928169–73 [Google Scholar]
  141. Forbes LR, Haczku A. 141.  2010. SP-D and regulation of the pulmonary innate immune system in allergic airway changes. Clin. Exp. Allergy 40:4547–62 [Google Scholar]
  142. Wert S, Jones T, Korfhagen T, Fisher J, Whitsett J. 142.  2000. Spontaneous emphysema in surfactant protein D gene-targeted mice. Chest 117:Suppl. 1248S [Google Scholar]
  143. Nakamura A, Ebina-Shibuya R, Itoh-Nakadai A, Muto A, Shima H. 143.  et al. 2013. Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J. Exp. Med. 210:112191–204 [Google Scholar]
  144. Guth AM, Janssen WJ, Bosio CM, Crouch EC, Henson PM, Dow SW. 144.  2009. Lung environment determines unique phenotype of alveolar macrophages. Am. J. Physiol. Lung. Cell Mol. Physiol. 296:6L936–46 [Google Scholar]
  145. Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K. 145.  et al. 2007. Alveolar macrophages are the primary interferon-α producer in pulmonary infection with RNA viruses. Immunity 27:2240–52 [Google Scholar]
  146. Archambaud C, Salcedo SP, Lelouard H, Devilard E, de Bovis B. 146.  et al. 2010. Contrasting roles of macrophages and dendritic cells in controlling initial pulmonary Brucella infection. Eur. J. Immunol. 40:123458–71 [Google Scholar]
  147. Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC. 147.  2010. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J. Virol. 84:157569–80 [Google Scholar]
  148. Maelfait J, Roose K, Bogaert P, Sze M, Saelens X. 148.  et al. 2012. A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection. PLOS Pathog. 8:3e1002570 [Google Scholar]
  149. Hussell T, Bell TJ. 149.  2014. Alveolar macrophages: plasticity in a tissue-specific context. Nat. Rev. Immunol. 14:281–93 [Google Scholar]
  150. Ishibashi H, Nakamura M, Komori A, Migita K, Shimoda S. 150.  2009. Liver architecture, cell function, and disease. Semin. Immunopathol. 31:3399–409 [Google Scholar]
  151. Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. 151.  2013. Kupffer Cells in the Liver New York: Wiley
  152. Toth CA, Thomas P. 152.  1992. Liver endocytosis and Kupffer cells. Hepatology 16:1255–66 [Google Scholar]
  153. Willekens FLA, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Döpp YAM. 153.  et al. 2005. Liver Kupffer cells rapidly remove red blood cell–derived vesicles from the circulation by scavenger receptors. Blood 105:52141–45 [Google Scholar]
  154. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ. 154.  et al. 2001. Identification of the haemoglobin scavenger receptor. Nature 409:6817198–201 [Google Scholar]
  155. Teitelbaum SL, Ross FP. 155.  2003. Genetic regulation of osteoclast development and function. Nat. Rev. Genet. 4:8638–49 [Google Scholar]
  156. Ortega N, Wang K, Ferrara N, Werb Z, Vu TH. 156.  2010. Complementary interplay between matrix metalloproteinase-9, vascular endothelial growth factor and osteoclast function drives endochondral bone formation. Dis. Model Mech. 3:3–4224–35 [Google Scholar]
  157. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S. 157.  et al. 1990. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345:6274442–44 [Google Scholar]
  158. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E. 158.  et al. 1999. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:6717315–23 [Google Scholar]
  159. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M. 159.  et al. 1997. Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature 386:662081–84 [Google Scholar]
  160. Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R. 160.  et al. 1994. C-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266:5184443–48 [Google Scholar]
  161. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G. 161.  et al. 1999. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J. Cell Biol. 145:3527–38 [Google Scholar]
  162. McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J. 162.  et al. 2000. Mice lacking β3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Investig. 105:4433–40 [Google Scholar]
  163. Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR. 163.  1992. Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J. Clin. Investig. 90:41622–27 [Google Scholar]
  164. Mann M, Barad O, Agami R, Geiger B, Hornstein E. 164.  2010. miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate. PNAS 107:3615804–9 [Google Scholar]
  165. Li YP, Chen W, Liang Y, Li E, Stashenko P. 165.  1999. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat. Genet. 23:4447–51 [Google Scholar]
  166. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K. 166.  et al. 2000. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141:93478–84 [Google Scholar]
  167. Binder NB, Niederreiter B, Hoffmann O, Stange R, Pap T. 167.  et al. 2009. Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis. Nat. Med. 15:4417–24 [Google Scholar]
  168. Seeling M, Hillenhoff U, David JP, Schett G, Tuckermann J. 168.  et al. 2013. Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice. PNAS 110:2610729–34 [Google Scholar]
  169. Kotani M, Kikuta J, Klauschen F, Chino T, Kobayashi Y. 169.  et al. 2013. Systemic circulation and bone recruitment of osteoclast precursors tracked by using fluorescent imaging techniques. J. Immunol. 190:2605–12 [Google Scholar]
  170. Merad M, Manz MG, Karsunky H, Wagers A, Peters W. 170.  et al. 2002. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3:121135–41 [Google Scholar]
  171. Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch U-K. 171.  et al. 2007. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat. Neurosci. 10:121544–53 [Google Scholar]
  172. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FMV. 172.  2007. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10:121538–43 [Google Scholar]
  173. Elmore MRP, Najafi AR, Koike MA, Dagher NN, Spangenberg EE. 173.  et al. 2014. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82:2380–97 [Google Scholar]
  174. Varvel NH, Grathwohl SA, Baumann F, Liebig C, Bosch A. 174.  et al. 2012. Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. PNAS 109:4418150–55 [Google Scholar]
  175. Tremblay M-È, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. 175.  2011. The role of microglia in the healthy brain. J. Neurosci. 31:4516064–69 [Google Scholar]
  176. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR. 176.  et al. 2012. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:4691–705 [Google Scholar]
  177. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M. 177.  et al. 2012. Synaptic pruning by microglia is necessary for normal brain development. Science 333:60481456–58 [Google Scholar]
  178. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G. 178.  et al. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17:3400–6 [Google Scholar]
  179. Sierra A, Encinas JM, Deudero JJP, Chancey JH, Enikolopov G. 179.  et al. 2010. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Stem Cell 7:4483–95 [Google Scholar]
  180. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J. 180.  et al. 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37:1050–60 [Google Scholar]
  181. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C. 181.  et al. 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13:753–60 [Google Scholar]
  182. Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. 182.  2010. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nat. Med. 17:164–70 [Google Scholar]
  183. Abutbul S, Shapiro J, Szaingurten-Solodkin I, Levy N, Carmy Y. 183.  et al. 2012. TGF-β signaling through SMAD2/3 induces the quiescent microglial phenotype within the CNS environment. Glia 60:71160–71 [Google Scholar]
  184. den Haan JMM, Kraal G. 184.  2012. Innate immune functions of macrophage subpopulations in the spleen. J. Innate Immun. 4:5–6437–45 [Google Scholar]
  185. Ganz T. 185.  2012. Macrophages and systemic iron homeostasis. J. Innate Immun. 4:5–6446–53 [Google Scholar]
  186. Kohyama M, Ise W, Edelson BT, Wilker PR, Hildner K. 186.  et al. 2009. Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457:7227318–21 [Google Scholar]
  187. Haldar M, Kohyama M, So AY-L, KC W, Wu X. 187.  et al. 2014. Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell 156:61223–34 [Google Scholar]
  188. Mebius RE, Kraal G. 188.  2005. Structure and function of the spleen. Nat. Rev. Immunol. 5:8606–16 [Google Scholar]
  189. Kraal G, Mebius R. 189.  2006. New insights into the cell biology of the marginal zone of the spleen. Int. Rev. Cytol. 250:175–215 [Google Scholar]
  190. Miyake Y, Asano K, Kaise H, Uemura M, Nakayama M, Tanaka M. 190.  2007. Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. J. Clin. Investig. 117:82268–78 [Google Scholar]
  191. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA. 191.  et al. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119:2299–309 [Google Scholar]
  192. A-Gonzalez N, Guillen JA, Gallardo G, Diaz M, de la Rosa JV. 192.  et al. 2013. The nuclear receptor LXRα controls the functional specialization of splenic macrophages. Nat. Immunol. 14:8831–39 [Google Scholar]
  193. McGaha TL, Chen Y, Ravishankar B, van Rooijen N, Karlsson MCI. 193.  2011. Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood 117:205403–12 [Google Scholar]
  194. Geijtenbeek TBH, Groot PC, Nolte MA, van Vliet SJ, Gangaram-Panday ST. 194.  et al. 2002. Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. Blood 100:82908–16 [Google Scholar]
  195. Kang Y-S, Kim JY, Bruening SA, Pack M, Charalambous A. 195.  et al. 2004. The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen. PNAS 101:1215–20 [Google Scholar]
  196. Mebius RE, Nolte MA, Kraal G. 196.  2004. Development and function of the splenic marginal zone. Crit. Rev. Immunol. 24:6449–64 [Google Scholar]
  197. Ato M, Nakano H, Kakiuchi T, Kaye PM. 197.  2004. Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19. J. Immunol. 173:84815–20 [Google Scholar]
  198. You Y, Myers RC, Freeberg L, Foote J, Kearney JF. 198.  et al. 2011. Marginal zone B cells regulate antigen capture by marginal zone macrophages. J. Immunol. 186:42172–81 [Google Scholar]
  199. Karlsson MCI, Guinamard R, Bolland S, Sankala M, Steinman RM, Ravetch JV. 199.  2003. Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone. J. Exp. Med. 198:2333–40 [Google Scholar]
  200. Koppel EA, Litjens M, van den Berg VC, van Kooyk Y, Geijtenbeek TBH. 200.  2008. Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B cells is essential to early IgM responses against Streptococcus pneumoniae. Mol. Immunol. 45:102881–87 [Google Scholar]
  201. Heikema AP, Bergman MP, Richards H, Crocker PR, Gilbert M. 201.  et al. 2010. Characterization of the specific interaction between sialoadhesin and sialylated Campylobacter jejuni lipooligosaccharides. Infect. Immun. 78:73237–46 [Google Scholar]
  202. Junt T, Moseman EA, Iannacone M, Massberg S, Lang PA. 202.  et al. 2007. Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450:7166110–14 [Google Scholar]
  203. Phan TG, Green JA, Gray EE, Xu Y, Cyster JG. 203.  2009. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat. Immunol. 10:7786–93 [Google Scholar]
  204. Backer R, Schwandt T, Greuter M, Oosting M, Jüngerkes F. 204.  et al. 2010. Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. PNAS 107:1216–21 [Google Scholar]
  205. Eloranta ML, Alm GV. 205.  1999. Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-α/β producers in mice upon intravenous challenge with herpes simplex virus. Scand. J. Immunol. 49:4391–94 [Google Scholar]
  206. Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M. 206.  et al. 2004. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:56741147–50 [Google Scholar]
  207. Ghosn EEB, Cassado AA, Govoni GR, Fukuhara T, Yang Y. 207.  et al. 2010. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. PNAS 107:62568–73 [Google Scholar]
  208. Cain DW, O'Koren EG, Kan MJ, Womble M, Sempowski GD. 208.  et al. 2013. Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages. J. Immunol. 191:94665–75 [Google Scholar]
  209. Okabe Y, Medzhitov R. 209.  2014. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157:832–44 [Google Scholar]
  210. Sathe P, Metcalf D, Vremec D, Naik SH, Langdon WY. 210.  et al. 2014. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor. Immunity 41:1104–15 [Google Scholar]
  211. Jaitin DA, Kenigsberg E, Keren-Shaul H, Elefant N, Paul F. 211.  et al. 2014. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343:6172776–79 [Google Scholar]
  212. Sica A, Mantovani A. 212.  2012. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Investig. 122:3787–95 [Google Scholar]
  213. Mosser DM, Edwards JP. 213.  2008. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8:12958–69 [Google Scholar]
  214. Martinez FO, Gordon S. 214.  2014. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 6:13 [Google Scholar]
  215. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW. 215.  et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:114–20 [Google Scholar]
  216. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W. 216.  et al. 2014. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40:2274–88 [Google Scholar]
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Macrophages: Development and Tissue Specialization
Annual Review of Immunology 33, 643 (2015); https://doi.org/10.1146/annurev-immunol-032414-112220
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