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Cited by 962Immune cells in cancerPhagocytosis and Immune RegulationImmune responses and vaccinations

Macrophages: Development and Tissue Specialization

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Varol, Chen, Mildner, Alexander, Jung, Steffen·2015·Annual Review of Immunology
DOI 10.1146/annurev-immunol-032414-112220
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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.

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  1. Medzhitov R. 2010. Inflammation 2010: new adventures of an old flame. Cell 140(6):771-76
  2. Davies LC, Jenkins SJ, Allen JE, Taylor PR. 2013. Tissue-resident macrophages. Nat. Immunol. 14(10):986-95
  3. Stefater JA III, Ren S, Lang RA, Duffield JS. 2011. Metchnikoff 's policemen: macrophages in develop- ment, homeostasis and regeneration. Trends Mol. Med. 17(12):743-52
  4. Jenkins SJ, Hume DA. 2014. Homeostasis in the mononuclear phagocyte system. Trends Immunol. 35(8):358-67
  5. van Furth R, Cohn ZA. 1968. The origin and kinetics of mononuclear phagocytes. J. Exp. Med. 128(3):415-35
  6. van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. 1972. The mononu- clear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 46(6):845-52
  7. 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(5):1142-62
  8. Mildner A, Jung S. 2014. Development and function of dendritic cell subsets. Immunity 40(5):642-56
  9. Palis J, Robertson S, Kennedy M, Wall C, Keller G. 1999. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126(22):5073-84
  10. Bertrand JY, Jalil A, Klaine M, Jung S, Cumano A, Godin I. 2005. Three pathways to mature macrophages in the early mouse yolk sac. Blood 106(9):3004-11
  11. Cumano A, Godin I. 2007. Ontogeny of the hematopoietic system. Annu. Rev. Immunol. 25(1):745-85
  12. Kumaravelu P, Hook L, Morrison AM, Ure J, Zhao S, 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(21):4891-99
  13. McGrath KE. 2002. Circulation is established in a stepwise pattern in the mammalian embryo. Blood 101(5):1669-75
  14. Lang RA, Bishop JM. 1993. Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74(3):453-62
  15. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, et al. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131(6):1164-78
  16. Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, et al. 2010. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116(5):829-40
  17. McKercher SR, Torbett BE, Anderson KL, Henkel GW, Vestal DJ, et al. 1996. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15(20):5647-58
  18. Hoeffel G, Wang Y, Greter M, See P, Teo P, 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(6):1167-81
  19. Sumner R, Crawford A, Mucenski M, Frampton J. 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(30):3335-42
  20. Lieu YK, Reddy EP. 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(51):21689-94
  21. Soza-Ried C, Hess I, Netuschil N, Schorpp M, Boehm T. 2010. Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. PNAS 107(40):17304-8
  22. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, et al. 2000. Analysis of fractalkine receptor CX 3 CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20(11):4106-14
  23. Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P, et al. 2006. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 311(5757):83-87
  24. Hettinger J, Richards DM, Hansson J, Barra MM, Joschko A-C, et al. 2013. Origin of monocytes and macrophages in a committed progenitor. Nat. Immunol. 14(8):821-30
  25. Jung K, Ohlrich B, Mildner D, Egger E. 1978. Apoenzymes of aspartate aminotransferase and alanine aminotransferase in the serum of healthy subjects. Z. Med. Lab. Diagn. 19(3):146-51
  26. Alliot F, Godin I, Pessac B. 1999. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Dev. Brain Res. 117(2):145-52
  27. Samokhvalov IM, Samokhvalova NI, Nishikawa S-I. 2007. Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 446(7139):1056-61
  28. Guilliams M, De Kleer I, Henri S, Post S, Vanhoutte L, 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(10):1977-92
  29. Seré K, Baek J-H, Ober-Bl öbaum J, M üller-Newen G, Tacke F, et al. 2012. Two distinct types of Langerhans cells populate the skin during steady state and inflammation. Immunity 37(5):905-16
  30. Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FMV. 2011. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14(9):1142-49
  31. Segura E, Amigorena S. 2013. Inflammatory dendritic cells in mice and humans. Trends Immunol. 34(9):440-45
  32. Avraham-Davidi I, Yona S, Grunewald M, Landsman L, Cochain C, et al. 2013. On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J. Exp. Med. 210(12):2611-25
  33. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A, et al. 2013. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39(3):599-610
  34. Priller J, Fl ügel A, Wehner T, Boentert M, Haas CA, et al. 2001. Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment. Nat. Med. 7(12):1356-61
  35. Kierdorf K, Katzmarski N, Haas CA, Prinz M. 2013. Bone marrow cell recruitment to the brain in the absence of irradiation or parabiosis bias. PLOS ONE 8(3):e58544
  36. Serbina NV, Pamer EG. 2006. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7(3):311-17
  37. Mizutani M, Pino PA, Saederup N, Charo IF, Ransohoff RM, Cardona AE. 2012. The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J. Immunol. 188(1):29-36
  38. Goldmann T, Wieghofer P, M üller PF, Wolf Y, Varol D, et al. 2013. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat. Neurosci. 16(11):1618-26
  39. Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B, et al. 2007. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J. Exp. Med. 204(1):171-80
  40. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, et al. 2010. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115(3):e10-19
  41. Mildner A, Chapnik E, Manor O, Yona S, Kim KW, et al. 2013. Mononuclear phagocyte microRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis. Blood 121(6):1016- 27
  42. Williams MJ. 2007. Drosophila hemopoiesis and cellular immunity. J. Immunol. 178(8):4711-16
  43. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, et al. 2009. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325(5940):612-16
  44. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, et al. 2009. In vivo analysis of dendritic cell development and homeostasis. Science 324(5925):392-97
  45. Passlick B, Flieger D, Ziegler-Heitbrock HW. 1989. Identification and characterization of a novel mono- cyte subpopulation in human peripheral blood. Blood 74(7):2527-34
  46. Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, et al. 2011. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C -monocytes. Nat. Immunol. 12(8):778-85
  47. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, et al. 2007. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317(5838):666-70
  48. Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, et al. 2013. Nr4a1-dependent Ly6C low monocytes monitor endothelial cells and orchestrate their disposal. Cell 153(2):362-75
  49. McNelis JC, Olefsky JM. 2014. Macrophages, immunity, and metabolic disease. Immunity 41(1):36-48
  50. Chawla A, Nguyen KD, Goh YPS. 2011. Macrophage-mediated inflammation in metabolic disease. Nat. Rev. Immunol. 11(11):738-49
  51. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, et al. 2004. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6(4):409-21
  52. Lin EY, Pollard JW. 2007. Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Res. 67(11):5064-66
  53. Laoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J, 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(1):24-30
  54. Movahedi K, Laoui D, Gysemans C, Baeten M, Stangé G, et al. 2010. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 70(14):5728-39
  55. Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, et al. 2014. The cellular and molecular origin of tumor-associated macrophages. Science 344(6186):921-25
  56. Escobar G, Moi D, Ranghetti A, Ozkal-Baydin P, Squadrito ML, et al. 2014. Genetic engineering of hematopoiesis for targeted IFN-α delivery inhibits breast cancer progression. Sci. Transl. Med. 6(217):217ra3
  57. Van Nguyen A, Pollard JW. 2002. Colony stimulating factor-1 is required to recruit macrophages into the mammary gland to facilitate mammary ductal outgrowth. Dev. Biol. 247(1):11-25
  58. Moore KJ, Sheedy FJ, Fisher EA. 2013. Macrophages in atherosclerosis: a dynamic balance. Nat. Rev. Immunol. 13(10):709-21
  59. Boring L, Gosling J, Chensue SW, Kunkel SL, Farese RV Jr, et al. 1997. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J. Clin. Investig. 100(10):2552-61
  60. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, et al. 2009. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113(4):963-72
  61. Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y, et al. 2013. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19(9):1166-72
  62. Vainchtein ID, Vinet J, Brouwer N, Brendecke S, Biagini G, et al. 2014. In acute experimental au- toimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia 62(10):1724-35
  63. Weber B, Saurer L, Schenk M, Dickgreber N, Mueller C. 2011. CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions. Eur. J. Immunol. 41(3):773-79
  64. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, et al. 2012. Ly6C hi monocytes in the in- flamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37(6):1076-90
  65. Zigmond E, Samia-Grinberg S, Pasmanik-Chor M, Brazowski E, Shibolet O, et al. 2014. Infiltrating monocyte-derived macrophages and resident Kupffer cells display different ontogeny and functions in acute liver injury. J. Immunol. 193(1):344-53
  66. Shechter R, London A, Varol C, Raposo C, Cusimano M, 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(7):e1000113
  67. Chazaud B. 2014. Macrophages: supportive cells for tissue repair and regeneration. Immunobiology 219(3):172-78
  68. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, et al. 2007. The healing my- ocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204(12):3037-47
  69. London A, Itskovich E, Benhar I, Kalchenko V, Mack M, et al. 2011. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med. 208(1):23-39
  70. Crane MJ, Daley JM, van Houtte O, Brancato SK, Henry WL, Albina JE. 2014. The monocyte to macrophage transition in the murine sterile wound. PLOS ONE 9(1):e86660
  71. Niess JH, Brand S, Gu X, Landsman L, Jung S, et al. 2005. CX 3 CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307(5707):254-58
  72. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y, et al. 2009. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31(3):502-12
  73. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, et al. 2009. Origin of the lamina propria dendritic cell network. Immunity 31(3):513-25 100.
  74. Jaensson E, Uronen-Hansson H, Pabst O, Eksteen B, Tian J, et al. 2008. Small intestinal CD103 + dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205(9):2139-49 101.
  75. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. 2004. Recognition of com- mensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118(2):229-41 102.
  76. Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP, et al. 2014. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343(6178):1249288 103.
  77. Seno H, Miyoshi H, Brown SL, Geske MJ, Colonna M, Stappenbeck TS. 2009. Efficient colonic mucosal wound repair requires Trem2 signaling. PNAS 106(1):256-61 104.
  78. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. 2012. Inflammation switches the differentiation program of Ly6C hi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J. Exp. Med. 209(1):139-55 105.
  79. Bogunovic M, Mortha A, Muller PA, Merad M. 2012. Mononuclear phagocyte diversity in the intestine. Immunol. Res. 54(1-3):37-49 108.
  80. Muller PA, Koscs ó B, Rajani GM, Stevanovic K, Berres M-L, et al. 2014. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158(2):300-13 109.
  81. Molawi K, Wolf Y, Kandalla PK, Favret J, Hagemeyer N, et al. 2014. Gradual replacement of embryo- derived cardiac macrophages with age. J. Exp. Med. 211(11):2151-58 113.
  82. Tagliani E, Shi C, Nancy P, Tay C-S, Pamer EG, Erlebacher A. 2011. Coordinate regulation of tissue macrophage and dendritic cell population dynamics by CSF-1. J. Exp. Med. 208(9):1901-16 114.
  83. Hashimoto K, Joshi SK, Koni PA. 2002. A conditional null allele of the major histocompatibility IA-beta chain gene. Genesis 32(2):152-53 115.
  84. Alliot F, Lecain E, Grima B, Pessac B. 1991. Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. PNAS 88(4):1541-45 116.
  85. Aziz A, Soucie E, Sarrazin S, Sieweke MH. 2009. MafB/c-Maf deficiency enables self-renewal of differ- entiated functional macrophages. Science 326(5954):867-71 117.
  86. Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, et al. 2011. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332(6035):1284-88 118.
  87. Ghigo C, Mondor I, Jorquera A, Nowak J, Wienert S, et al. 2013. Multicolor fate mapping of Langerhans cell homeostasis. J. Exp. Med. 210(9):1657-64 119.
  88. Barth MW, Hendrzak JA, Melnicoff MJ, Morahan PS. 1995. Review of the macrophage disappearance reaction. J. Leukoc. Biol. 57(3):361-67 120.
  89. Davies LC, Rosas M, Smith PJ, Fraser DJ, Jones SA, Taylor PR. 2011. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur. J. Immunol. 41(8):2155-64 121.
  90. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR III, et al. 2013. Microglia promote learning- dependent synapse formation through brain-derived neurotrophic factor. Cell 155(7):1596-609 122.
  91. Gautier EL, Ivanov S, Williams JW, Huang SCC, Marcelin G, et al. 2014. Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. J. Exp. Med. 211(8):1525-31 124.
  92. Jenkins SJ, Ruckerl D, Thomas GD, Hewitson JP, Duncan S, et al. 2013. IL-4 directly signals tissue- resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J. Exp. Med. 210(11):2477-91 125.
  93. Bogdan C, Vodovotz Y, Nathan C. 1991. Macrophage deactivation by interleukin 10. J. Exp. Med. 174(6):1549-55 130.
  94. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, et al. 2000. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290(5497):1768-71 134.
  95. Snelgrove RJ, Goulding J, Didierlaurent AM, Lyonga D, Vekaria S, et al. 2008. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat. Immunol. 9(9):1074-83 135.
  96. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159(6):1312-26 137.
  97. Beck JM, Young VB, Huffnagle GB. 2012. The microbiome of the lung. Transl. Res. 160(4):258-66 138.
  98. Guilliams M, Lambrecht BN, Hammad H. 2013. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 6(3):464-73 139.
  99. Gollwitzer ES, Saglani S, Trompette A, Yadava K, Sherburn R, et al. 2014. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20(6):642-47 140.
  100. Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, et al. 2003. Loss of integrin αvβ6-mediated TGF-β activation causes Mmp12-dependent emphysema. Nature 422(6928):169-73 141.
  101. Forbes LR, Haczku A. 2010. SP-D and regulation of the pulmonary innate immune system in allergic airway changes. Clin. Exp. Allergy 40(4):547-62 142.
  102. Nakamura A, Ebina-Shibuya R, Itoh-Nakadai A, Muto A, Shima H, et al. 2013. Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J. Exp. Med. 210(11):2191-204 144.
  103. Guth AM, Janssen WJ, Bosio CM, Crouch EC, Henson PM, Dow SW. 2009. Lung environment deter- mines unique phenotype of alveolar macrophages. Am. J. Physiol. Lung. Cell Mol. Physiol. 296(6):L936-46 145.
  104. Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K, et al. 2007. Alveolar macrophages are the primary interferon-α producer in pulmonary infection with RNA viruses. Immunity 27(2):240-52 146.
  105. Archambaud C, Salcedo SP, Lelouard H, Devilard E, de Bovis B, et al. 2010. Contrasting roles of macrophages and dendritic cells in controlling initial pulmonary Brucella infection. Eur. J. Immunol. 40(12):3458-71 147.
  106. Tate MD, Pickett DL, van Rooijen N, Brooks AG, Reading PC. 2010. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J. Virol. 84(15):7569-80 148.
  107. Maelfait J, Roose K, Bogaert P, Sze M, Saelens X, et al. 2012. A20 (Tnfaip3) deficiency in myeloid cells protects against influenza A virus infection. PLOS Pathog. 8(3):e1002570 149.
  108. Hussell T, Bell TJ. 2014. Alveolar macrophages: plasticity in a tissue-specific context. Nat. Rev. Immunol. 14(2):81-93 150.
  109. Ishibashi H, Nakamura M, Komori A, Migita K, Shimoda S. 2009. Liver architecture, cell function, and disease. Semin. Immunopathol. 31(3):399-409 151.
  110. Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. 2013. Kupffer Cells in the Liver. New York: Wiley 152.
  111. Toth CA, Thomas P. 1992. Liver endocytosis and Kupffer cells. Hepatology 16(1):255-66 153.
  112. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, et al. 2001. Identification of the haemoglobin scavenger receptor. Nature 409(6817):198-201 155.
  113. Teitelbaum SL, Ross FP. 2003. Genetic regulation of osteoclast development and function. Nat. Rev. Genet. 4(8):638-49 156.
  114. Ortega N, Wang K, Ferrara N, Werb Z, Vu TH. 2010. Complementary interplay between matrix metalloproteinase-9, vascular endothelial growth factor and osteoclast function drives endochondral bone formation. Dis. Model Mech. 3(3-4):224-35 157.
  115. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, et al. 1999. OPGL is a key regulator of osteoclasto- genesis, lymphocyte development and lymph-node organogenesis. Nature 397(6717):315-23 159.
  116. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M, et al. 1997. Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature 386(6620):81-84 160.
  117. Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, et al. 1994. C-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266(5184):443-48 161.
  118. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, et al. 1999. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J. Cell Biol. 145(3):527-38 162.
  119. McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, et al. 2000. Mice lacking β3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Investig. 105(4):433-40 163.
  120. Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR. 1992. Requirement of pp60 c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J. Clin. Investig. 90(4):1622-27 164.
  121. Mann M, Barad O, Agami R, Geiger B, Hornstein E. 2010. miRNA-based mechanism for the commit- ment of multipotent progenitors to a single cellular fate. PNAS 107(36):15804-9 165.
  122. Li YP, Chen W, Liang Y, Li E, Stashenko P. 1999. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat. Genet. 23(4):447-51 166.
  123. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, et al. 2000. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141(9):3478- 84 167.
  124. Binder NB, Niederreiter B, Hoffmann O, Stange R, Pap T, et al. 2009. Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis. Nat. Med. 15(4):417-24 168.
  125. Seeling M, Hillenhoff U, David JP, Schett G, Tuckermann J, et al. 2013. Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice. PNAS 110(26):10729-34 169.
  126. Kotani M, Kikuta J, Klauschen F, Chino T, Kobayashi Y, et al. 2013. Systemic circulation and bone recruitment of osteoclast precursors tracked by using fluorescent imaging techniques. J. Immunol. 190(2):605-12 170.
  127. Merad M, Manz MG, Karsunky H, Wagers A, Peters W, et al. 2002. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3(12):1135-41 171.
  128. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FMV. 2007. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10(12):1538-43 173.
  129. Varvel NH, Grathwohl SA, Baumann F, Liebig C, Bosch A, et al. 2012. Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. PNAS 109(44):18150-55 175.
  130. Tremblay M-È, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. 2011. The role of microglia in the healthy brain. J. Neurosci. 31(45):16064-69 176.
  131. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, et al. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17(3):400-6 179.
  132. Abutbul S, Shapiro J, Szaingurten-Solodkin I, Levy N, Carmy Y, et al. 2012. TGF-β signaling through SMAD2/3 induces the quiescent microglial phenotype within the CNS environment. Glia 60(7):1160-71 184. den Haan JMM, Kraal G. 2012. Innate immune functions of macrophage subpopulations in the spleen. J. Innate Immun. 4(5-6):437-45 185.
  133. Mebius RE, Kraal G. 2005. Structure and function of the spleen. Nat. Rev. Immunol. 5(8):606-16 189.
  134. Miyake Y, Asano K, Kaise H, Uemura M, Nakayama M, Tanaka M. 2007. Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. J. Clin. Investig. 117(8):2268-78 191.
  135. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, et al. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119(2):299-309 192.
  136. A-Gonzalez N, Guillen JA, Gallardo G, Diaz M, de la Rosa JV, et al. 2013. The nuclear receptor LXRα controls the functional specialization of splenic macrophages. Nat. Immunol. 14(8):831-39 193.
  137. McGaha TL, Chen Y, Ravishankar B, van Rooijen N, Karlsson MCI. 2011. Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood 117(20):5403-12 194.
  138. Geijtenbeek TBH, Groot PC, Nolte MA, van Vliet SJ, Gangaram-Panday ST, et al. 2002. Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. Blood 100(8):2908-16 195.
  139. Kang Y-S, Kim JY, Bruening SA, Pack M, Charalambous A, 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(1):215-20 196.
  140. Mebius RE, Nolte MA, Kraal G. 2004. Development and function of the splenic marginal zone. Crit. Rev. Immunol. 24(6):449-64 197.
  141. Ato M, Nakano H, Kakiuchi T, Kaye PM. 2004. Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19. J. Immunol. 173(8):4815-20 198.
  142. You Y, Myers RC, Freeberg L, Foote J, Kearney JF, et al. 2011. Marginal zone B cells regulate antigen capture by marginal zone macrophages. J. Immunol. 186(4):2172-81 199.
  143. Karlsson MCI, Guinamard R, Bolland S, Sankala M, Steinman RM, Ravetch JV. 2003. Macrophages con- trol the retention and trafficking of B lymphocytes in the splenic marginal zone. J. Exp. Med. 198(2):333- 40 200.
  144. Koppel EA, Litjens M, van den Berg VC, van Kooyk Y, Geijtenbeek TBH. 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(10):2881-87 201.
  145. Heikema AP, Bergman MP, Richards H, Crocker PR, Gilbert M, et al. 2010. Characterization of the specific interaction between sialoadhesin and sialylated Campylobacter jejuni lipooligosaccharides. Infect. Immun. 78(7):3237-46 202.
  146. Phan TG, Green JA, Gray EE, Xu Y, Cyster JG. 2009. Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Nat. Immunol. 10(7):786-93 204.
  147. Backer R, Schwandt T, Greuter M, Oosting M, J üngerkes F, et al. 2010. Effective collaboration between marginal metallophilic macrophages and CD8 + dendritic cells in the generation of cytotoxic T cells. PNAS 107(1):216-21 205.
  148. Eloranta ML, Alm GV. 1999. Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-α/β producers in mice upon intravenous challenge with her- pes simplex virus. Scand. J. Immunol. 49(4):391-94 206.
  149. Cain DW, O'Koren EG, Kan MJ, Womble M, Sempowski GD, et al. 2013. Identification of a tissue- specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages. J. Immunol. 191(9):4665-75 209.
  150. Sathe P, Metcalf D, Vremec D, Naik SH, Langdon WY, et al. 2014. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor. Immunity 41(1):104-15 211.
  151. Jaitin DA, Kenigsberg E, Keren-Shaul H, Elefant N, Paul F, et al. 2014. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343(6172):776-79 212.
  152. Sica A, Mantovani A. 2012. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Investig. 122(3):787-95 213.
  153. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, et al. 2014. Macrophage activation and polar- ization: nomenclature and experimental guidelines. Immunity 41(1):14-20 216.
  154. Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, et al. 2014. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40(2):274-88

Cited by

Sorted by citations

Authors
Varol, C., Mildner, A., & Jung, S.
Affiliations
  • Tel Aviv University (IL)
  • Weizmann Institute of Science (IL)
Corresponding author
Jung, Steffen
ORCID
Venue
Annual Review of Immunology
Publisher
Annual Reviews
Published
2015-03-21
Volume
33
Issue
1
Pages
643-675
ISSN
  • 0732-0582 (ISSN-L)
  • 1545-3278
DOI
10.1146/annurev-immunol-032414-112220
OpenAlex
W2158070898
Cited by
962
References
45
Citations by year
2026: 47 · 2025: 97 · 2024: 105 · 2023: 77 · 2022: 105 · 2021: 99 · 2020: 123 · 2019: 89 · 2018: 75 · 2017: 77 · 2016: 50 · 2015: 17
FWCI
6.87
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
tissue-resident macrophages, macrophage development, macrophage self-renewal, tissue specialization, macrophage heterogeneity, histogenesis
MeSH terms
Animals, Cell Differentiation, Humans, Immunity, Macrophages, Organ Specificity, Phenotype

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