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Cited by 989Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchMultiple Sclerosis Research Studies

Astrocyte Crosstalk in CNS Inflammation

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Linnerbauer, Mathias, Wheeler, Michael A., Quintana, Francisco J.·2020·Neuron
DOI 10.1016/j.neuron.2020.08.012PMC PMC7704785
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Abstract

Astrocytes control multiple processes in the nervous system in health and disease. It is now clear that specific astrocyte subsets or activation states are associated with specific genomic programs and functions. The advent of novel genomic technologies has enabled rapid progress in the characterization of astrocyte heterogeneity and its control by astrocyte interactions with other cells in the central nervous system (CNS). In this review, we provide an overview of the multifaceted roles of astrocytes in the context of CNS inflammation, highlighting recent discoveries on astrocyte subsets and their regulation. We explore mechanisms of crosstalk between astrocytes and other cells in the CNS in the context of neuroinflammation and neurodegeneration and discuss how these interactions shape pathological outcomes.

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  • Activated microglia and astrocytes can phagocytize Aβ through multiple receptors to protect neurons, but failure to clear aggregates leads to persistent chronic inflammation and release of proinflammatory/toxic products (cytokines, chemokines, ROS, NO), amplifying immune responses and neurotoxicity.

    “Activated microglia and astrocytes can phagocytize Aβ through multiple receptors to protect neurons,33,34 but failure to clear the aggregates leads to persistent chronic inflammation and the release of a variety of proinflammatory and toxic products, including cytokines, chemokines, reactive oxygen species (ROS) and nitric oxide (NO), which amplify immune responses and lead to neurotoxicity.35”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [33]

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Research works printed but not linked: 166

  1. Allen M, Zou F, Chai HS, Younkin C, Crook J, Pankratz V, Carrasquillo M, Rowley C, Nair A, Middha S, (2012a). Novel Late-Onset Alzheimer’s Disease Loci Variants Associate with Brain Gene Expression (S54.001). Neurology 78, S54.001– S054.001. PMC3398432 22722634
  2. Allen NJ, and Eroglu C (2017). Cell biology of astrocyte-synapse interactions. Neuron 96, 697– 708. 29096081 PMC5687890
  3. Allen NJ, and Lyons DA (2018). Glia as architects of central nervous system formation and function. Science 362, 181– 185. 30309945 PMC6292669
  4. Alvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonnière L, Bernard M, (2011). The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence. Science 334, 1727– 1731. 22144466
  5. Anderson MA, Ao Y, and Sofroniew MV (2014). Heterogeneity of reactive astrocytes. Neurosci Lett 565, 23– 29. 24361547 PMC3984948
  6. Anderson MA, O’Shea TM, Burda JE, Ao Y, Barlatey SL, Bernstein AM, Kim JH, James ND, Rogers A, Kato B, (2018). Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature 561, 396– 400. 30158698 PMC6151128
  7. Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, Mahase S, Dutta DJ, Seto J, Kramer EG, (2012). Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest 122, 2454– 2468. 22653056 PMC3386814
  8. Atreya R, Mudter J, Finotto S, Müllberg J, Jostock T, Wirtz S, Schütz M, Bartsch B, Holtmann M, Becker C, (2000). Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo. Nature Medicine 6, 583– 588. 10802717
  9. Bayraktar OA, Bartels T, Holmqvist S, Kleshchevnikov V, Martirosyan A, Polioudakis D, Ben Haim L, Young AMH, Batiuk MY, Prakash K, (2020). Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nature Neuroscience 23, 500– 509. 32203496 PMC7116562
  10. Beurel E (2011). HDAC6 Regulates LPS-Tolerance in Astrocytes. PLOS ONE 6, e25804. 22022450 PMC3192131
  11. Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, Clercq ED, Vescovi A, Bagetta G, Kollias G, Meldolesi J, and Volterra A (2001). CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity. Nature Neuroscience 4, 702– 710. 11426226
  12. Blank T, and Prinz M (2014). NF-κB signaling regulates myelination in the CNS. Front Mol Neurosci 7. 24904273 PMC4033361
  13. Brambilla R, Bracchi-Ricard V, Hu W-H, Frydel B, Bramwell A, Karmally S, Green EJ, and Bethea JR (2005). Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. The Journal of Experimental Medicine 202, 145– 156. 15998793 PMC2212896
  14. Brambilla R, Dvoriantchikova G, Barakat D, Ivanov D, Bethea JR, and Shestopalov VI (2012). Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. Journal of Neuroinflammation 9, 213. 22963651 PMC3490907
  15. Brambilla R, Morton PD, Ashbaugh JJ, Karmally S, Lambertsen KL, and Bethea JR (2014). Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination. Glia 62, 452– 467. 24357067
  16. Brambilla R, Persaud T, Hu X, Karmally S, Shestopalov VI, Dvoriantchikova G, Ivanov D, Nathanson L, Barnum SR, and Bethea JR (2009). Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol 182, 2628– 2640. 19234157 PMC4291126
  17. Butts BD, Houde C, and Mehmet H (2008). Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease. Cell Death & Differentiation 15, 1178– 1186. 18483490
  18. Chandel NS, Trzyna WC, McClintock DS, and Schumacker PT (2000). Role of Oxidants in NF-κB Activation and TNF-α Gene Transcription Induced by Hypoxia and Endotoxin. The Journal of Immunology 165, 1013– 1021. 10878378
  19. Chao C-C, Gutiérrez-Vázquez C, Rothhammer V, Mayo L, Wheeler MA, Tjon EC, Zandee SEJ, Blain M, de Lima KA, Takenaka MC, (2019). Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS. Cell 179, 1483– 1498.e1422. 31813625 PMC6936326
  20. Chatterjee S, Kolmakova A, and Rajesh M (2008). Regulation of lactosylceramide synthase (glucosylceramide beta1-->4 galactosyltransferase); implication as a drug target. Curr Drug Targets 9, 272– 281. 18393821
  21. Chen X, Sun YC, Zhan H, Kebschull JM, Fischer S, Matho K, Huang ZJ, Gillis J, and Zador AM (2019). High-Throughput Mapping of Long-Range Neuronal Projection Using In Situ Sequencing. Cell 179, 772– 786 e719. 31626774 PMC7836778
  22. Chisholm NC, Henderson ML, Selvamani A, Park MJ, Dindot S, Miranda RC, and Sohrabji F (2015). Histone methylation patterns in astrocytes are influenced by age following ischemia. Epigenetics 10, 142– 152. 25565250 PMC4622874
  23. Choi C, Park JY, Lee J, Lim J-H, Shin E-C, Ahn YS, Kim C-H, Kim S-J, Kim J-D, Choi IS, and Choi I-H (1999). Fas Ligand and Fas Are Expressed Constitutively in Human Astrocytes and the Expression Increases with IL-1, IL-6, TNF-α, or IFN-γ. The Journal of Immunology 162, 1889– 1895. 9973455
  24. Choi JW, Gardell SE, Herr DR, Rivera R, Lee C-W, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G, and Chun J (2011). FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proceedings of the National Academy of Sciences 108, 751– 756. PMC3021041 21177428
  25. Chow BW, Nunez V, Kaplan L, Granger AJ, Bistrong K, Zucker HL, Kumar P, Sabatini BL, and Gu C (2020). Caveolae in CNS arterioles mediate neurovascular coupling. Nature 579, 106– 110. 32076269 PMC7060132
  26. Christopherson KS, Ullian EM, Stokes CCA, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, and Barres BA (2005). Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120, 421– 433. 15707899
  27. Colombo E, Cordiglieri C, Melli G, Newcombe J, Krumbholz M, Parada LF, Medico E, Hohlfeld R, Meinl E, and Farina C (2012). Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration. The Journal of Experimental Medicine 209, 521– 535. 22393127 PMC3302220
  28. Colombo E, and Farina C (2016). Astrocytes: Key Regulators of Neuroinflammation. Trends in Immunology 37, 608– 620. 27443914
  29. Colonna M, and Butovsky O (2017). Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annual Review of Immunology 35, 441– 468. PMC8167938 28226226
  30. Correa F, Mallard C, Nilsson M, and Sandberg M (2011). Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: restoring effects of inhibitors of HDACs, p38 MAPK and GSK3β. Neurobiol Dis 44, 142– 151. 21757005 PMC3341174
  31. Deneen B, Ho R, Lukaszewicz A, Hochstim CJ, Gronostajski RM, and Anderson DJ (2006). The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron 52, 953– 968. 17178400
  32. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, and Eggan K (2007). Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10, 608– 614. 17435754 PMC3139463
  33. Diaz-Castro B, Gangwani MR, Yu X, Coppola G, and Khakh BS (2019). Astrocyte molecular signatures in Huntington’s disease. Sci Transl Med 11. 31619545
  34. Domingues HS, Portugal CC, Socodato R, and Relvas JB (2016). Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair. Front Cell Dev Biol 4. 27551677 PMC4923166
  35. Elain G, Jeanneau K, Rutkowska A, Mir AK, and Dev KK (2014). The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes. Glia 62, 725– 735. 24677511
  36. Eng C-HL, Lawson M, Zhu Q, Dries R, Koulena N, Takei Y, Yun J, Cronin C, Karp C, Yuan G, and Cai L (2019). Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568, 235– 239. 30911168 PMC6544023
  37. Fan G, Martinowich K, Chin MH, He F, Fouse SD, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, (2005). DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development 132, 3345– 3356. 16014513
  38. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, and Sofroniew MV (2004). Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24, 2143– 2155. 14999065 PMC6730429
  39. Ferraiuolo L, Higginbottom A, Heath PR, Barber S, Greenald D, Kirby J, and Shaw PJ (2011). Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain: A Journal of Neurology 134, 2627– 2641. PMC3170534 21908873
  40. Fields RD (2013). Neuroscience: Map the other brain. Nature 501, 25– 27. 24010144 PMC5017588
  41. Fields RD, and Stevens-Graham B (2002). New Insights into Neuron-Glia Communication. Science 298, 556– 562. 12386325 PMC1226318
  42. Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, and Rocca MA (2018). Multiple sclerosis. Nat Rev Dis Primers 4, 43. 30410033
  43. Fontana A, Fierz W, and Wekerle H (1984). Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 307, 273– 276. 6198590
  44. Fuccillo M, Joyner AL, and Fishell G (2006). Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nature Reviews Neuroscience 7, 772– 783. 16988653
  45. Garner KM, Amin R, Johnson RW, Scarlett EJ, and Burton MD (2018). Microglia priming by interleukin-6 signaling is enhanced in aged mice. J Neuroimmunol 324, 90– 99. 30261355 PMC6699492
  46. Gerard C, and Rollins BJ (2001). Chemokines and disease. Nature Immunology 2, 108– 115. 11175802
  47. Glass CK, and Saijo K (2010). Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nature Reviews Immunology 10, 365– 376. 20414208
  48. Gold R, Schmied M, Tontsch U, Hartung HP, Wekerle H, Toyka KV, and Lassmann H (1996). Antigen presentation by astrocytes primes rat T lymphocytes for apoptotic cell death. A model for T-cell apoptosis in vivo. Brain: A Journal of Neurology 119 (Pt 2), 651– 659. 8800954
  49. Goldmann T, and Prinz M (2013). Role of microglia in CNS autoimmunity. Clin Dev Immunol 2013, 208093. 23840238 PMC3694374
  50. Gomez-Rivera F, Raphael I, and Forsthuber T (2017). Signaling via TNFR2 mediates CNS remyelination in EAE through regulation of oligodendrocyte progenitor cells. The Journal of Immunology 198, 219.214– 219.214.
  51. Greenberg MVC, and Bourc’his D (2019). The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol 20, 590– 607. 31399642
  52. Gruol DL, and Nelson TE (1997). Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 15, 307– 339. 9457704
  53. Gu X-L, Long C-X, Sun L, Xie C, Lin X, and Cai H (2010). Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain 3, 12. 20409326 PMC2873589
  54. Gutiérrez-Vázquez C, and Quintana FJ (2018). Regulation of the Immune Response by the Aryl Hydrocarbon Receptor. Immunity 48, 19– 33. 29343438 PMC5777317
  55. Habib N, McCabe C, Medina S, Varshavsky M, Kitsberg D, Dvir-Szternfeld R, Green G, Dionne D, Nguyen L, and Marshall JL (2020). Disease-associated astrocytes in Alzheimer’s disease and aging. Nature Neuroscience, 1– 6. PMC9262034 32341542
  56. Haim LB, and Rowitch DH (2017). Functional diversity of astrocytes in neural circuit regulation. Nature Reviews Neuroscience 18, 31– 41. 27904142
  57. Hashioka S, Klegeris A, Schwab C, Yu S, and McGeer PL (2010). Differential expression of interferon-y receptor on human glial cells in vivo and in vitro. Journal of Neuroimmunology 225, 91– 99. 20554027
  58. Hatada I, Namihira M, Morita S, Kimura M, Horii T, and Nakashima K (2008). Astrocyte-Specific Genes Are Generally Demethylated in Neural Precursor Cells Prior to Astrocytic Differentiation. PLOS ONE 3, e3189. 18784832 PMC2527128
  59. Heink S, Yogev N, Garbers C, Herwerth M, Aly L, Gasperi C, Husterer V, Croxford AL, Möller-Hackbarth K, Bartsch HS, (2017). Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells. Nat Immunol 18, 74– 85. 27893700 PMC5164931
  60. Heneka MT, Golenbock DT, and Latz E (2015). Innate immunity in Alzheimer’s disease. Nature Immunology 16, 229– 236. 25689443
  61. Huang D, Wang J, Kivisakk P, Rollins BJ, and Ransohoff RM (2001). Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis. The Journal of Experimental Medicine 193, 713– 726. 11257138 PMC2193420
  62. Huang L, Kebschull JM, Furth D, Musall S, Kaufman MT, Churchland AK, and Zador AM (2020). BRICseq Bridges Brain-wide Interregional Connectivity to Neural Activity and Gene Expression in Single Animals. Cell 182, 177– 188 e127. 32619423 PMC7771207
  63. Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, Haroutunian V, Zhu J, Donovan MJ, Sharp AJ, and Casaccia P (2014). Epigenome-wide differences in pathology-free regions of multiple sclerosis–affected brains. Nature Neuroscience 17, 121– 130. 24270187 PMC3934491
  64. Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kriegstein AR, and Alvarez-Buylla A (2011). Persistent Sonic hedgehog Signaling in Adult Brain Determines Neural Stem Cell Positional Identity. Neuron 71, 250– 262. 21791285 PMC3346180
  65. Jakel S, Agirre E, Mendanha Falcao A, van Bruggen D, Lee KW, Knuesel I, Malhotra D, Ffrench-Constant C, Williams A, and Castelo-Branco G (2019). Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature. PMC6544546 30747918
  66. Katoh Y, Ikura T, Hoshikawa Y, Tashiro S, Ito T, Ohta M, Kera Y, Noda T, and Igarashi K (2011). Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol Cell 41, 554– 566. 21362551
  67. Katsuoka F, and Yamamoto M (2016). Small Maf proteins (MafF, MafG, MafK): History, structure and function. Gene 586, 197– 205. 27058431 PMC4911266
  68. Kawai T, and Akira S (2007). Signaling to NF-κB by Toll-like receptors. Trends in Molecular Medicine 13, 460– 469. 18029230
  69. Kebschull JM, Garcia da Silva P, Reid AP, Peikon ID, Albeanu DF, and Zador AM (2016). High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA. Neuron 91, 975– 987. 27545715 PMC6640135
  70. Khakh BS, and Deneen B (2019). The Emerging Nature of Astrocyte Diversity. Annu Rev Neurosci 42, 187– 207. 31283899
  71. Kim RY, Hoffman AS, Itoh N, Ao Y, Spence R, Sofroniew MV, and Voskuhl RR (2014). Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 274, 53– 61. 25005117 PMC4343306
  72. Kim S, Steelman AJ, Koito H, and Li J (2011). Astrocytes promote TNF-mediated toxicity to oligodendrocyte precursors. Journal of Neurochemistry 116, 53– 66. 21044081 PMC3057964
  73. Kipnis J (2016). Multifaceted interactions between adaptive immunity and the central nervous system. Science 353, 766– 771. 27540163 PMC5590839
  74. Koch MW, Metz LM, and Kovalchuk O (2013). Epigenetic changes in patients with multiple sclerosis. Nature Reviews Neurology 9, 35– 43. 23165337
  75. Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, (2006). Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129, 200– 211. 16280350
  76. Krumbholz M, Theil D, Derfuss T, Rosenwald A, Schrader F, Monoranu C-M, Kalled SL, Hess DM, Serafini B, Aloisi F, (2005). BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. The Journal of Experimental Medicine 201, 195– 200. 15642740 PMC2212784
  77. Kular L, Liu Y, Ruhrmann S, Zheleznyakova G, Marabita F, Gomez-Cabrero D, James T, Ewing E, Linden M, Gornikiewicz B, (2018). DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis. Nature Communications 9, 2397. PMC6008330 29921915
  78. Li W, Maeda Y, Ming X, Cook S, Chapin J, Husar W, and Dowling P (2002). Apoptotic death following Fas activation in human oligodendrocyte hybrid cultures. J Neurosci Res 69, 189– 196. 12111800
  79. Liddelow SA, and Barres BA (2017). Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity 46, 957– 967. 28636962
  80. Liedtke W, Edelmann W, Chiu FC, Kucherlapati R, and Raine CS (1998). Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion. The American Journal of Pathology 152, 251– 259. 9422542 PMC1858102
  81. Lin CCJ, Yu K, Hatcher A, Huang TW, Lee HK, Carlson J, Weston MC, Chen F, Zhang Y, Zhu W, (2017). Identification of diverse astrocyte populations and their malignant analogs. Nat Neurosci 20, 396– 405. 28166219 PMC5824716
  82. Locatelli G, Theodorou D, Kendirli A, Jordao MJC, Staszewski O, Phulphagar K, Cantuti-Castelvetri L, Dagkalis A, Bessis A, Simons M, (2018). Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model. Nat Neurosci 21, 1196– 1208. 30127427
  83. Locatelli G, Wörtge S, Buch T, Ingold B, Frommer F, Sobottka B, Krüger M, Karram K, Bühlmann C, Bechmann I, (2012). Primary oligodendrocyte death does not elicit anti-CNS immunity. Nat Neurosci 15, 543– 550. 22366759
  84. Loo G.v., Lorenzi RD, Schmidt H, Huth M, Mildner A, Schmidt-Supprian M, Lassmann H, Prinz MR, and Pasparakis M (2006). Inhibition of transcription factor NF-κB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nature Immunology 7, 954– 961. 16892069
  85. Magistretti PJ, and Allaman I (2018). Lactate in the brain: from metabolic end-product to signalling molecule. Nature Reviews Neuroscience 19, 235– 249. 29515192
  86. Matos M, Augusto E, Oliveira CR, and Agostinho P (2008). Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 156, 898– 910. 18790019
  87. Mayo L, Trauger SA, Blain M, Nadeau M, Patel B, Alvarez JI, Mascanfroni ID, Yeste A, Kivisäkk P, Kallas K, (2014). Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nature Medicine 20, 1147– 1156. PMC4255949 25216636
  88. McQualter JL, Darwiche R, Ewing C, Onuki M, Kay TW, Hamilton JA, Reid HH, and Bernard CCA (2001). Granulocyte Macrophage Colony-Stimulating FactorA New Putative Therapeutic Target in Multiple Sclerosis. The Journal of Experimental Medicine 194, 873– 882. 11581310 PMC2193476
  89. Merlini M, Meyer EP, Ulmann-Schuler A, and Nitsch RM (2011). Vascular ß-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAß mice. Acta Neuropathol 122, 293– 311. 21688176 PMC3168476
  90. Mills Ko E, Ma JH, Guo F, Miers L, Lee E, Bannerman P, Burns T, Ko D, Sohn J, Soulika AM, and Pleasure D (2014). Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model. Journal of Neuroinflammation 11, 105. 24924222 PMC4066277
  91. Moffitt JR, Bambah-Mukku D, Eichhorn SW, Vaughn E, Shekhar K, Perez JD, Rubinstein ND, Hao J, Regev A, Dulac C, and Zhuang X (2018). Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science 362. PMC6482113 30385464
  92. Molofsky AV, and Deneen B (2015). Astrocyte development: A Guide for the Perplexed. Glia 63, 1320– 1329. 25963996
  93. Molofsky AV, Kelley KW, Tsai H-H, Redmond SA, Chang SM, Madireddy L, Chan JR, Baranzini SE, Ullian EM, and Rowitch DH (2014). Astrocyte-encoded positional cues maintain sensorimotor circuit integrity. Nature 509, 189– 194. 24776795 PMC4057936
  94. Moreno M, Bannerman P, Ma J, Guo F, Miers L, Soulika AM, and Pleasure D (2014). Conditional Ablation of Astroglial CCL2 Suppresses CNS Accumulation of M1 Macrophages and Preserves Axons in Mice with MOG Peptide EAE. J Neurosci 34, 8175– 8185. 24920622 PMC4051973
  95. Mount CW, Yalcin B, Cunliffe-Koehler K, Sundaresh S, and Monje M (2019). Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity. Elife 8. PMC6800000 31625910
  96. Moyon S, Dubessy AL, Aigrot MS, Trotter M, Huang JK, Dauphinot L, Potier MC, Kerninon C, Melik Parsadaniantz S, Franklin RJM, and Lubetzki C (2015). Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration. J Neurosci 35, 4– 20. 25568099 PMC6605244
  97. Mu Y, Bennett DV, Rubinov M, Narayan S, Yang CT, Tanimoto M, Mensh BD, Looger LL, and Ahrens MB (2019). Glia Accumulate Evidence that Actions Are Futile and Suppress Unsuccessful Behavior. Cell 178, 27– 43 e19. 31230713
  98. Nagai J, Rajbhandari AK, Gangwani MR, Hachisuka A, Coppola G, Masmanidis SC, Fanselow MS, and Khakh BS (2019). Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell 177, 1280– 1292 e1220. 31031006 PMC6526045
  99. Neher JJ, and Cunningham C (2019). Priming Microglia for Innate Immune Memory in the Brain. Trends in Immunology 40, 358– 374. 30833177
  100. Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, (2020). Defining trained immunity and its role in health and disease. Nat Rev Immunol 20, 375– 388. 32132681 PMC7186935
  101. Nguyen PT, Dorman LC, Pan S, Vainchtein ID, Han RT, Nakao-Inoue H, Taloma SE, Barron JJ, Molofsky AB, Kheirbek MA, and Molofsky AV (2020). Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell 182, 388– 403 e315. 32615087 PMC7497728
  102. Niu J, Tsai H-H, Hoi KK, Huang N, Yu G, Kim K, Baranzini SE, Xiao L, Chan JR, and Fancy SPJ (2019). Aberrant oligodendroglial-vascular interactions disrupt the Blood Brain Barrier triggering CNS inflammation. Nature Neuroscience 22, 709– 718. 30988524 PMC6486410
  103. Nott A, and Glass CK (2018). Immune memory in the brain. Nature 556, 312– 313. 29662132
  104. O’Callaghan JP, Kelly KA, VanGilder RL, Sofroniew MV, and Miller DB (2014). Early Activation of STAT3 Regulates Reactive Astrogliosis Induced by Diverse Forms of Neurotoxicity. PLOS ONE 9, e102003. 25025494 PMC4098997
  105. Oh SW, Harris JA, Ng L, Winslow B, Cain N, Mihalas S, Wang Q, Lau C, Kuan L, Henry AM, (2014). A mesoscale connectome of the mouse brain. Nature 508, 207– 214. 24695228 PMC5102064
  106. Öhman A, and Forsgren L (2015). NMR metabonomics of cerebrospinal fluid distinguishes between Parkinson’s disease and controls. Neurosci Lett 594, 36– 39. 25817365
  107. Omari KM, John GR, Sealfon SC, and Raine CS (2005). CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis. Brain 128, 1003– 1015. 15774504
  108. Pardo AC, Wong V, Benson LM, Dykes M, Tanaka K, Rothstein JD, and Maragakis NJ (2006). Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) mice. Exp Neurol 201, 120– 130. 16753145
  109. Paul D, Ge S, Lemire Y, Jellison ER, Serwanski DR, Ruddle NH, and Pachter JS (2014). Cell- selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation. J Neuroinflammation 11, 10. 24444311 PMC3906899
  110. Peferoen L, Kipp M, van der Valk P, van Noort JM, and Amor S (2014). Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology 141, 302– 313. 23981039 PMC3930369
  111. Pfrieger FW, and Barres BA (1997). Synaptic Efficacy Enhanced by Glial Cells in Vitro. Science 277, 1684– 1687. 9287225
  112. Pitt D, Werner P, and Raine CS (2000). Glutamate excitotoxicity in a model of multiple sclerosis. Nature Medicine 6, 67– 70. 10613826
  113. Polyzos AA, Lee DY, Datta R, Hauser M, Budworth H, Holt A, Mihalik S, Goldschmidt P, Frankel K, Trego K, (2019). Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice. Cell metabolism 29, 1258– 1273.e1211. 30930170 PMC6583797
  114. Ponath G, Ramanan S, Mubarak M, Housley W, Lee S, Sahinkaya FR, Vortmeyer A, Raine CS, and Pitt D (2017). Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology. Brain: A Journal of Neurology 140, 399– 413. PMC5841057 28007993
  115. Prinz M, Jung S, and Priller J (2019). Microglia Biology: One Century of Evolving Concepts. Cell 179, 292– 311. 31585077
  116. Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-wit D, Xiao J, Lu Y, Giltiay N, Liu J, (2007). The adaptor Act1 is required for interleukin 17–dependent signaling associated with autoimmune and inflammatory disease. Nature Immunology 8, 247– 256. 17277779
  117. Ramesh G, Benge S, Pahar B, and Philipp MT (2012). A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi. Journal of Neuroinflammation 9, 1– 15. 22524232 PMC3416675
  118. Ransohoff RM, and Engelhardt B (2012). The anatomical and cellular basis of immune surveillance in the central nervous system. Nature Reviews Immunology 12, 623– 635. 22903150
  119. Reich DS, Lucchinetti CF, and Calabresi PA (2018). Multiple Sclerosis. N Engl J Med 378, 169– 180. 29320652 PMC6942519
  120. Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E, Vanderburg CR, Welch J, Chen LM, Chen F, and Macosko EZ (2019). Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science 363, 1463– 1467. 30923225 PMC6927209
  121. Rosen H, and Goetzl EJ (2005). Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nature Reviews Immunology 5, 560– 570. 15999095
  122. Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao C-C, Ardura-Fabregat A, Lima K.A.d., Gutiérrez-Vázquez C, Hewson P, Staszewski O, (2018). Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724– 728. 29769726 PMC6422159
  123. Rothhammer V, Kenison JE, Tjon E, Takenaka MC, Lima K.A.d., Borucki DM, Chao C-C, Wilz A, Blain M, Healy L, (2017). Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation. Proceedings of the National Academy of Sciences 114, 2012– 2017. PMC5338419 28167760
  124. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao C-C, Patel B, Yan R, Blain M, (2016). Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and CNS inflammation via the aryl hydrocarbon receptor. Nature medicine 22, 586– 597. PMC4899206 27158906
  125. Rothhammer V, and Quintana FJ (2015). Control of autoimmune CNS inflammation by astrocytes. Semin Immunopathol 37, 625– 638. 26223505 PMC4618768
  126. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, and Glass CK (2009). A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137, 47– 59. 19345186 PMC2754279
  127. Salisbury RL, and Sulentic CEW (2015). The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3’ Immunoglobulin Heavy Chain Regulatory Region. Toxicol Sci 148, 443– 459. 26377645 PMC5009439
  128. Samoilova EB, Horton JL, Hilliard B, Liu TS, and Chen Y (1998). IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 161, 6480– 6486. 9862671
  129. Sanchis P, Fernádez-Gayol O, Comes G, Escrig A, Giralt M, Palmiter RD, and Hidalgo J (2020). Interleukin-6 Derived from the Central Nervous System May Influence the Pathogenesis of Experimental Autoimmune Encephalomyelitis in a Cell-Dependent Manner. Cells 9. PMC7072597 32023844
  130. Santello M, and Volterra A (2009). Synaptic modulation by astrocytes via Ca2+-dependent glutamate release. Neuroscience 158, 253– 259. 18455880
  131. Savarin C, Hinton DR, Valentin-Torres A, Chen Z, Trapp BD, Bergmann CC, and Stohlman SA (2015). Astrocyte response to IFN-γ limits IL-6-mediated microglia activation and progressive autoimmune encephalomyelitis. Journal of Neuroinflammation 12. 25896970 PMC4410573
  132. Smith HL, Freeman OJ, Butcher AJ, Holmqvist S, Humoud I, Schatzl T, Hughes DT, Verity NC, Swinden DP, Hayes J, (2020). Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration. Neuron 105, 855– 866 e855. 31924446 PMC7054837
  133. Sofroniew MV (2009). Molecular dissection of reactive astrogliosis and glial scar formation. Trends in Neurosciences 32, 638– 647. 19782411 PMC2787735
  134. Sofroniew MV (2015b). Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16, 249– 263. 25891508 PMC5253239
  135. Solano RM, Casarejos MJ, Menéndez-Cuervo J, Rodriguez-Navarro JA, García de Yébenes J, and Mena MA (2008). Glial Dysfunction in Parkin Null Mice: Effects of Aging. The Journal of Neuroscience 28, 598– 611. 18199761 PMC6670347
  136. Soos JM, Morrow J, Ashley TA, Szente BE, Bikoff EK, and Zamvil SS (1998). Astrocytes Express Elements of the Class II Endocytic Pathway and Process Central Nervous System Autoantigen for Presentation to Encephalitogenic T Cells. The Journal of Immunology 161, 5959– 5966. 9834077
  137. Staszewski O, and Prinz M (2014). Glial epigenetics in neuroinflammation and neurodegeneration. Cell Tissue Res 356, 609– 616. 24652504
  138. Sun D, and Wekerle H (1986). Ia-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presenting astrocytes. Nature 320, 70– 72. 2419764
  139. Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, and Taga T (2001). DNA Methylation Is a Critical Cell-Intrinsic Determinant of Astrocyte Differentiation in the Fetal Brain. Developmental Cell 1, 749– 758. 11740937
  140. Toft-Hansen H, Füchtbauer L, and Owens T (2011). Inhibition of reactive astrocytosis in established experimental autoimmune encephalomyelitis favors infiltration by myeloid cells over T cells and enhances severity of disease. Glia 59, 166– 176. 21046558
  141. Tong X, Ao Y, Faas GC, Nwaobi SE, Xu J, Haustein MD, Anderson MA, Mody I, Olsen ML, Sofroniew MV, and Khakh BS (2014). Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat Neurosci 17, 694– 703. 24686787 PMC4064471
  142. Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, Tenney A, Murnen AT, Fancy SP, Merkle F, (2012). Regional astrocyte allocation regulates CNS synaptogenesis and repair. Science 337, 358– 362. 22745251 PMC4059181
  143. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, and Fugger L (2008). Interleukin-17 Production in Central Nervous System-Infiltrating T Cells and Glial Cells Is Associated with Active Disease in Multiple Sclerosis. The American Journal of Pathology 172, 146– 155. 18156204 PMC2189615
  144. Vainchtein ID, Chin G, Cho FS, Kelley KW, Miller JG, Chien EC, Liddelow SA, Nguyen PT, Nakao-Inoue H, Dorman LC, (2018). Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development. Science (New York, NY) 359, 1269– 1273. PMC6070131 29420261
  145. Valentin-Torres A, Savarin C, Barnett J, and Bergmann CC (2018). Blockade of sustained tumor necrosis factor in a transgenic model of progressive autoimmune encephalomyelitis limits oligodendrocyte apoptosis and promotes oligodendrocyte maturation. Journal of Neuroinflammation 15, 1– 16. 29690885 PMC5916830
  146. Vogel CFA, Khan EM, Leung PSC, Gershwin ME, Chang WLW, Wu D, Haarmann-Stemmann T, Hoffmann A, and Denison MS (2014). Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB. J Biol Chem 289, 1866– 1875. 24302727 PMC3894361
  147. Vogel CFA, Sciullo E, Li W, Wong P, Lazennec G, and Matsumura F (2007). RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol 21, 2941– 2955. 17823304 PMC2346533
  148. Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LBJ, Tiwari-Woodruff S, and Sofroniew MV (2009). Reactive Astrocytes Form Scar-Like Perivascular Barriers to Leukocytes during Adaptive Immune Inflammation of the CNS. J Neurosci 29, 11511– 11522. 19759299 PMC2768309
  149. Wallace VA, and Raff MC (1999). A role for Sonic hedgehog in axon-to-astrocyte signalling in the rodent optic nerve. Development 126, 2901– 2909. 10357934
  150. Walz W (2000). Role of astrocytes in the clearance of excess extracellular potassium. Neurochemistry International 36, 291– 300. 10732996
  151. Wang X, Deckert M, Xuan NT, Nishanth G, Just S, Waisman A, Naumann M, and Schlüter D (2013a). Astrocytic A20 ameliorates experimental autoimmune encephalomyelitis by inhibiting NF-κB- and STAT1-dependent chemokine production in astrocytes. Acta Neuropathol 126, 711– 724. 24077734
  152. Wang X, Haroon F, Karray S, Deckert M, and Schlüter D (2013b). Astrocytic Fas ligand expression is required to induce T-cell apoptosis and recovery from experimental autoimmune encephalomyelitis. European Journal of Immunology 43, 115– 124. 23011975
  153. Wheeler MA, Clark IC, Tjon EC, Li Z, Zandee SEJ, Couturier CP, Watson BR, Scalisi G, Alkwai S, Rothhammer V, (2020a). MAFG-driven astrocytes promote CNS inflammation. Nature 578, 593– 599. 32051591 PMC8049843
  154. Wheeler MA, Clark IC, Tjon EC, Li Z, Zandee SEJ, Couturier CP, Watson BR, Scalisi G, Alkwai S, Rothhammer V, (2020b). MAFG-driven astrocytes promote CNS inflammation. Nature. PMC8049843 32051591
  155. Wheeler MA, Jaronen M, Covacu R, Zandee SEJ, Scalisi G, Rothhammer V, Tjon EC, Chao C-C, Kenison JE, Blain M, (2019). Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation. Cell 176, 581– 596.e518. 30661753 PMC6440749
  156. Wheeler MA, and Quintana FJ (2019). Regulation of Astrocyte Functions in Multiple Sclerosis. Cold Spring Harbor perspectives in medicine 9. PMC6314073 29358321
  157. Wheeler MA, Rothhammer V, and Quintana FJ (2017). Control of immune-mediated pathology via the aryl hydrocarbon receptor. J Biol Chem 292, 12383– 12389. 28615443 PMC5535014
  158. White RE, Yin FQ, and Jakeman LB (2008). TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice. Exp Neurol 214, 10– 24. 18647603 PMC2895965
  159. Yang JF, Tao HQ, Liu YM, Zhan XX, Liu Y, Wang XY, Wang JH, Mu LL, Yang LL, Gao ZM, (2012). Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis (EAE) in mice. Clinical & Experimental Immunology 170, 254– 265. 23121666 PMC3518885
  160. Yeste A, Takenaka MC, Mascanfroni ID, Nadeau M, Kenison JE, Patel B, Tukpah A-M, Babon JAB, DeNicola M, Kent SC, (2016). Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci Signal 9, ra61– ra61. 27330188
  161. Yi H, Bai Y, Zhu X, lin L, Zhao L, Wu X, Buch S, Wang L, Chao J, and Yao H (2014). IL-17A Induces MIP-1α Expression in Primary Astrocytes via Src/MAPK/PI3K/NF-kB Pathways: Implications for Multiple Sclerosis. J Neuroimmune Pharmacol 9, 629– 641. 24989845
  162. Yu X, Taylor AMW, Nagai J, Golshani P, Evans CJ, Coppola G, and Khakh BS (2018). Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior. Neuron 99, 1170– 1187 e1179. 30174118 PMC6450394
  163. Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, and Barres BA (2012). Genomic analysis of reactive astrogliosis. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 32, 6391– 6410. PMC3480225 22553043
  164. Zeis T, Enz L, and Schaeren-Wiemers N (2016). The immunomodulatory oligodendrocyte. Brain Res 1641, 139– 148. 26423932
  165. Zeis T, and Schaeren-Wiemers N (2008). Lame ducks or fierce creatures? The role of oligodendrocytes in multiple sclerosis. J Mol Neurosci 35, 91– 100. 18278568
  166. Zeisel A, Muñoz-Manchado AB, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, Marques S, Munguba H, He L, Betsholtz C, (2015). Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science (New York, NY) 347, 1138– 1142. 25700174

Cited by

Sorted by citations

Authors
Linnerbauer, M., Wheeler, M. A., & Quintana, F. J.
Affiliations
  • Brigham and Women's Hospital (US)
  • Broad Institute (US)
Corresponding author
Quintana, Francisco J.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2020-11
Volume
108
Issue
4
Pages
608-622
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2020.08.012
PMC
PMC7704785
OpenAlex
W3083733923
Cited by
989
References
41
Citations by year
2026: 151 · 2025: 233 · 2024: 212 · 2023: 164 · 2022: 141 · 2021: 86 · 2020: 1 · 2012: 1
FWCI
10.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • International Progressive MS Alliance (F32NS101790, 1K99NS114111)
  • Dana-Farber Cancer Institute (T32CA207201)
  • National Multiple Sclerosis Society
  • National Institutes of Health (AI126880, NS102807, RG4111A1, JF2161-A-5)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
astrocytes, astrocyte heterogeneity, neuroinflammation, neurodegeneration
MeSH terms
Animals, Astrocytes, Cell Communication, Central Nervous System, Humans, Inflammation, Models, Neurological

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