Microglia in health and disease

Cold Spring Harbor Perspectives in Biology

Volumn 8, Issue 1, 2016, Pages

  Ransohoff, Richard M ^a   El Khoury, Joseph ^b  

^a LERNER RESEARCH INSTITUTE   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR; CX3CR1 PROTEIN, HUMAN; FRACTALKINE;

ALZHEIMER DISEASE; CENTRAL NERVOUS SYSTEM DISEASE; GENETICS; HUMAN; METABOLISM; MICROGLIA; MULTIPLE SCLEROSIS; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; CENTRAL NERVOUS SYSTEM DISEASES; CHEMOKINE CX3CL1; HUMANS; MICROGLIA; MULTIPLE SCLEROSIS; RECEPTORS, CHEMOKINE; SIGNAL TRANSDUCTION;

EID: 84953307232     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a020560     Document Type: Article

References (107)

1. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM. 2007. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10: 1538-1543.
2. Alliot F, Lecain E, Grima B, Pessac B. 1991. Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. ProcNatl Acad Sci 88: 1541- 1545.
3. Alliot F, Godin I, Pessac B. 1999. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 117: 145-152.
4. 3C motif.Nature 385: 640-644.
5. Beutner C, Linnartz-Gerlach B, Schmidt SV, Beyer M,Mallmann MR, Staratschek-Jox A, Schultze JL, Neumann H. 2013. Unique transcriptome signature of mouse microglia. Glia 61: 1429-1442.
6. Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT. 2010. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68: 19-31.
7. Boehme SA, Lio FM, Maciejewski-Lenoir D, Bacon KB, Conlon PJ. 2000. The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia. J Immunol 165: 397-403.
8. Bradshaw EM, Chibnik LB, Keenan BT, Ottoboni L, Raj T, Tang A, Rosenkrantz LL, Imboywa S, Lee M, Von Korff A, et al. 2013. CD33 Alzheimer's disease locus: Altered monocyte function and amyloid biology. Nat Neurosci 16: 848-850.
9. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B,Wu PM, Doykan CE, et al. 2014. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17: 131-143.
10. Cardona AE, Sasse ME, Liu L, Cardona SM, Mizutani M, Savarin C,Hu T, Ransohoff RM. 2008. Scavenging roles of chemokine receptors: Chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues. Blood 112: 256-263.
11. Catalano M, Lauro C, Cipriani R, Chece G, Ponzetta A, Di Angelantonio S, Ragozzino D, Limatola C. 2013. CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes. J Neuroimmunol 263: 75-82.
12. Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ. 2000. Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20: RC87.
13. CharoIF, Ransohoff RM. 2006. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354: 610-621.
14. Chen SK, Tvrdik P, Peden E, Cho S, Wu S, Spangrude G, Capecchi MR. 2010. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell 141: 775-785.
15. Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O'Keeffe S, Phatnani HP,Muratet M, Carroll MC, Levy S, Tavazoie S, et al. 2013. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep 4: 385-401.
16. Cipriani R, Villa P, Chece G, Lauro C, Paladini A, Micotti E, Perego C, De Simoni MG, Fredholm BB, Eusebi F, et al. 2011. CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. J Neurosci 31: 16327-16335.
17. Clark AK, Yip PK, Malcangio M. 2009. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci 29: 6945-6954.
18. Cook DN, Chen SC, Sullivan LM, Manfra DJ, Wiekowski MT, Prosser DM, Vassileva G, Lira SA. 2001. Generation and analysis of mice lacking the chemokine fractalkine. Mol Cell Biol 21: 3159-3165.
19. Cuzner ML, Hayes GM,Newcombe J,Woodroofe MN. 1988. The nature of inflammatory components during demyelination in multiple sclerosis. J Neuroimmunol 20: 203- 209.
20. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8: 752-758.
21. del Río-Hortega Pd. 1918. Noticia de un nuevo y fácil mé- todo para la coloración de la neuroglia y el tejido conjuntivo [A new and easiest approach for staining glia and connective tissue]. Trab Lab Inv Biol 15: 367-378.
22. del Río-Hortega Pd. 1919. El "tercer elemento" de los centros nerviosos. Poder fagocitario y mivilidad de la microglía [The "third element" of the central nervous system. Phagocytic power of microglia]. Bol Soc Esp Biol 8: 62- 82.
23. del Río-Hortega Pd. 1920. La microglía y su transformación en células en bastoncito y cuerpos granuloadiposos [Transformation in the microglial cell bodies]. Trab Lab Inv Biol 18: 37-82.
24. del Río-Hortega Pd. 1921. Histogénesis y evolución normal, éxodo y distrubución regional de la microglía [Evolution and regional distribution of microglia].Mem Real Soc Esp Hist Nat 11: 213-268.
25. Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG, Kipnis J. 2012.Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484: 105-109.
26. El Khoury J. 2010. Neurodegeneration and the neuroimmune system. Nat Med 16: 1369-1370.
27. El Khoury J, Hickman SE, Thomas CA, Cao L, Silverstein SC, Loike JD. 1996. Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils. Nature 382: 716- 719.
28. El Khoury JB,Moore KJ,Means TK, Leung J, Terada K, Toft M, Freeman MW, Luster AD. 2003. CD36 mediates the innate host response to β-amyloid. J ExpMed 197: 1657- 1666.
29. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD. 2007. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer- like disease. Nat Med 13: 432-438.
30. 3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med 188: 1413-1419.
31. Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM. 1998. Microglial response to amyloid plaques in APPsw transgenic mice. AmJ Pathol 152: 307- 317.
32. Frenkel D, Wilkinson K, Zhao L, Hickman SE, Means TK, Puckett L, Farfara D, Kingery ND,Weiner HL, El Khoury J. 2013. Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer's-like disease progression. Nat Commun 4: 2030.
33. Froininann C. 1878. Untersuchungen über die Gewebveränderungen bei der multiplen sklerose des gehirns und ruckenmarks [Studies in multiple sclerosis of the brain]. Gustav Fischer, Jena, Germany.
34. Garcia JA, Pino PA, Mizutani M, Cardona SM, Charo IF, Ransohoff RM, Forsthuber TG, Cardona AE. 2013. Regulation of adaptive immunity by the fractalkine receptor during autoimmune inflammation. J Immunol 191: 1063-1072.
35. Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW. 2001. Tumor necrosis factorα- converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). J Biol Chem 276: 37993-38001.
36. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330: 841-845.
37. Giulian D, Baker TJ. 1986. Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 6: 2163-2178.
38. Goldmann T,Wieghofer P, Müller PF,Wolf Y, Varol D, Yona S, Brendecke SM, Kierdorf K, Staszewski O, Datta M, et al. 2013. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci 16: 1618-1626.
39. Graeber MB, Ló pez-Redondo F, Ikoma E, Ishikawa M, Imai Y, Nakajima K, Kreutzberg GW, Kohsaka S. 1998. The microglia/macrophage response in the neonatal rat facial nucleus following axotomy. Brain Res 813: 241-253.
40. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J, Leboeuf M, Kündig TM, Frei K, Ginhoux F, Merad M, et al. 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37: 1050-1060.
41. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, et al. 2013. TREM2 variants in Alzheimer's disease. N Engl J Med 368: 117-127.
42. Harrison JK, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara RK, Streit WJ, Salafranca MN, Adhikari S, Thompson DA, et al. 1998. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci 95: 10896-10901.
43. Haskell CA, Cleary MD, Charo IF. 1999. Molecular uncoupling of fractalkine-mediated cell adhesion and signal transduction. Rapid flow arrest of CX3CR1-expressing cells is independent of G-protein activation. J Biol Chem 274: 10053-10058.
44. Haskell CA, Cleary MD, Charo IF. 2000. Unique role of the chemokine domain of fractalkine in cell capture. Kinetics of receptor dissociation correlatewith cell adhesion. J Biol Chem 275: 34183-34189.
45. 3CR1 reveals a role for fractalkine in cardiac allograft rejection. J Clin Invest 108: 679-688.
46. Hawkes CA, McLaurin J. 2009. Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy. ProcNatl Acad Sci 106: 1261- 1266.
47. 12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9: 1512-1519.
48. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, et al. 2013. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493: 674-678.
49. Hickman SE, Allison EK, El Khoury J. 2008. Microglial dysfunction and defective β-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 28: 8354- 8360.
50. Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, El Khoury J. 2013. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16: 1896-1905.
51. Hoover DM, Mizoue LS, Handel TM, Lubkowski J. 2000. The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement. J Biol Chem 275: 23187-23193.
52. Horuk R. 1994. Molecular properties of the chemokine receptor family. Trends Pharmacol Sci 15: 159-165.
53. Huang D, Shi FD, Jung S, Pien GC,Wang J, Salazar-Mather TP, He TT, Weaver JT, Ljunggren HG, Biron CA, et al. 2006. The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J 20: 896-905.
54. Hume DA, Perry VH, Gordon S. 1983. Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: Phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers. J Cell Biol 97: 253-257.
55. Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V, et al. 2003. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 102: 1186-1195.
56. Imai Y, Ibata I, Ito D, Ohsawa K, Kohsaka S. 1996. A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun 224: 855-862.
57. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, et al. 2012. Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med 368: 107-116.
58. 3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20: 4106-4114.
59. Kierdorf K, Prinz M. 2013. Factors regulating microglia activation. Front Cell Neurosci 7: 44.
60. 3C chemokine fractalkine. Blood 118: e156-e167.
61. Kumar-Singh S, Pirici D,McGowan E, Serneels S, Ceuterick C, Hardy J, Duff K, DicksonD, Van Broeckhoven C. 2005. Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls. Am J Pathol 167: 527-543.
62. 3CL1-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180: 7590-7596.
63. Lauro C, Cipriani R, Catalano M, Trettel F, Chece G, Brusadin V, Antonilli L, van Rooijen N, Eusebi F, Fredholm BB, et al. 2010. Adenosine A1 receptors and microglial cells mediate CX3CL1-induced protection of hippocampal neurons against Glu-induced death. Neuropsychopharmacology 35: 1550-1559.
64. Lebson L, Nash K, Kamath S, Herber D, Carty N, Lee DC, Li Q, Szekeres K, Jinwal U, Koren J, et al. 2010. Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice. J Neurosci 30: 9651-9658.
65. Lee S, Varvel NH, Konerth ME, Xu G, Cardona AE, Ransohoff RM, Lamb BT. 2010. CX3CR1 deficiency alters microglial activation and reduces β-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol 177: 2549-2562.
66. Liu Z, Condello C, Schain A, Harb R, Grutzendler J. 2010. CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-β phagocytosis. J Neurosci 30: 17091-17101.
67. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA. 1998. Impaired Blymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4 or SDF-1 deficient mice. Proc Natl Acad Sci 95: 9448-9453.
68. McGeer EG, McGeer PL. 2010. Neuroinflammation in Alzheimer's disease and mild cognitive impairment: A field in its infancy. J Alzheimers Dis 19: 355-361.
69. McGeer PL, Itagaki S, Tago H, McGeer EG. 1987. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79: 195-200.
70. McKercher SR, Torbett BE, Anderson KL, HenkelGW, Vestal DJ, Baribault H, Klemsz M, Feeney AJ,Wu GE, Paige CJ, et al. 1996. Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J 15: 5647-5658.
71. Meda L, Cassatella MA, Szendrei GI, Otvos L Jr, Baron P, Villalba M, Ferrari D, Rossi F. 1995. Activation of microglial cells by β-amyloid protein and interferon-g. Nature 374: 647-650.
72. 3CR1. Biochemistry 38: 1402-1414.
73. 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: 29-36.
74. Morganti JM, Nash KR, Grimmig BA, Ranjit S, Small B, Bickford PC, Gemma C. 2012. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson's disease. J Neurosci 32: 14592- 14601.
75. Nakayama T, Watanabe Y, Osio N, Higuchi T, Shigeta A, Mizuguchi N, Katou F, Hashimoto K, Kawada A, Yoshie O. 2010. Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1. J Immunol 185: 6472-6479.
76. Nash KR, Lee DC, Hunt JB Jr, Morganti JM, Selenica ML, Moran P, Reid P, Brownlow M, Guang-Yu Yang C, Savalia M, et al. 2013. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy. Neurobiol Aging 34: 1540-1548.
77. Nimmerjahn A, Kirchhoff F, Helmchen F. 2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308: 1314-1318.
78. Paolicelli RC, Gross CT. 2011. Microglia in development: Linking brain wiring to brain environment. Neuron Glia Biol 7: 77-83.
79. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, et al. 2011. Synaptic pruning by microglia is necessary for normal brain development. Science 333: 1456- 1458.
80. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR III, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. 2013. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155: 1596-1609.
81. Perry VH, Hume DA, Gordon S. 1985. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15: 313-326.
82. Prinz M, Priller J, Sisodia SS, Ransohoff RM. 2011. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14: 1227-1235.
83. Ransohoff RM. 2005. Selective leukocyte chemoattractants emerge from the primeval sup(ernatants). J Immunol 175: 5567-5568.
84. Ransohoff RM, Cardona AE. 2010. The myeloid cells of the central nervous system parenchyma. Nature 468: 253- 262.
85. Ransohoff RM, Stevens B. 2011. Neuroscience. How many cell types does it take to wire a brain? Science 333: 1391- 1392.
86. Rawji KS, Yong VW. 2013. The benefits and detriments of macrophages/microglia in models of multiple sclerosis. Clin Dev Immunol 2013: 948976.
87. RotA, von Andrian UH. 2004. Chemokines in innate and adaptive host defense: Basic chemokinese grammar for immune cells. Annu Rev Immunol 22: 891-928.
88. Rozemuller JM, Eikelenboom P, Stam FC. 1986. Role of microglia in plaque formation in senile dementia of the Alzheimer type. An immunohistochemical study. Virchows Arch B Cell Pathol Incl Mol Pathol 51: 247-254.
89. Schafer DP, Stevens B. 2015. Microglia function in central nervous system development and plasticity. Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a020545.
90. SchaferDP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B. 2012. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74: 1-15.
91. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, et al. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336: 86-90.
92. Shaftel SS, Kyrkanides S, Olschowka JA, Miller JN, Johnson RE, O'Banion MK. 2007. Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117: 1595-1604.
93. Soriano SG, Amaravadi LS,Wang YF, Zhou H, Yu GX, Tonra JR, Fairchild-Huntress V, Fang Q, Dunmore JH, Huszar D, et al. 2002. Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. J Neuroimmunol 125: 59-65.
94. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, et al. 2010. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11: 155-161.
95. 3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: Kinetics and cellular origin. J Neuroinflammation 2: 17.
96. TooyamaI, Kimura H, Akiyama H, McGeer PL. 1990. Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer's disease. Brain Res 523: 273-280.
97. Tremblay ME, Lowery RL, Majewska AK. 2010. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8: e1000527.
98. TrippRA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ. 2001. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol 2: 732-738.
99. Tsou CL, Haskell CA, Charo IF. 2001. Tumor necrosis factorα- converting enzyme mediates the inducible cleavage of fractalkine. J Biol Chem 276: 44622-44626.
100. Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, Yamashita T. 2013. Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci 16: 543-551.
101. WalzW, Ilschner S, Ohlemeyer C, Banati R, Kettenmann H. 1993. Extracellular ATP activates a cation conductance and a Kβ conductance in cultured microglial cells from mouse brain. J Neurosci 13: 4403-4411.
102. Wang Y, Szretter KJ, VermiW, Gilfillan S, Rossini C, Cella M, Barrow AD, Diamond MS, Colonna M. 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol 13: 753-760.
103. Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC, et al. 2014. Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211: 1533- 1549.
104. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, et al. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 17: 400-406.
105. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. 1998. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393: 595-599.
106. Zucker-Franklin D,Warfel A, Grusky G, Frangione B, Teitel D. 1987. Novel monocyte-like properties of microglial/ astroglial cells. Constitutive secretion of lysozyme and cystatin-C. Lab Invest 57: 176-185.
107. Zujovic V, Schussler N, Jourdain D, Duverger D, Taupin V. 2001. In vivo neutralization of endogenous brain fractalkine increases hippocampal TNF-α and 8-isoprostane production induced by intracerebroventricular injection of LPS. J Neuroimmunol 115: 135-143.