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Seminars in Immunopathology

Erschienen in:

01.11.2015 | Review

Control of autoimmune CNS inflammation by astrocytes

verfasst von: Veit Rothhammer, Francisco J. Quintana

Erschienen in: Seminars in Immunopathology | Ausgabe 6/2015

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Abstract

Multiple sclerosis is a neurologic disease caused by immune cell infiltration into the central nervous system, resulting in gray and white matter inflammation, progressive demyelination, and neuronal loss. Astrocytes, the most abundant cell population in the central nervous system (CNS), have been considered inert scaffold or housekeeping cells for many years. However, recently, it has become clear that this cell population actively modulates the immune response in the CNS at multiple levels. While being exposed to a plethora of cytokines during ongoing autoimmune inflammation, astrocytes modulate local CNS inflammation by secreting cytokines and chemokines, among other factors. This review article gives an overview of the most recent understanding about cytokine networks operational in astrocytes during autoimmune neuroinflammation and highlights potential targets for immunomodulatory therapies for multiple sclerosis.

Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B (1998) Activation of the MHC class II transactivator CIITA by interferon-gamma requires cooperative interaction between Stat1 and USF-1. Immunity 8:157–166PubMedCrossRef

Hashioka S, Klegeris A, Schwab C, Yu S, McGeer PL (2010) Differential expression of interferon-gamma receptor on human glial cells in vivo and in vitro. J Neuroimmunol 225:91–99. doi:10.1016/j.jneuroim.2010.04.023 PubMedCrossRef

Nikcevich KM, Gordon KB, Tan L, Hurst SD, Kroepfl JF, Gardinier M, Barrett TA, Miller SD (1997) IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells. J Immunol 158:614–621PubMed

Sun D, Coleclough C, Whitaker JN (1997) Nonactivated astrocytes downregulate T cell receptor expression and reduce antigen-specific proliferation and cytokine production of myelin basic protein (MBP)-reactive T cells. J Neuroimmunol 78:69–78PubMedCrossRef

Gold R, Schmied M, Tontsch U, Hartung HP, Wekerle H, Toyka KV, Lassmann H (1996) Antigen presentation by astrocytes primes rat T lymphocytes for apoptotic cell death. A model for T-cell apoptosis in vivo. Brain 119(Pt 2):651–659PubMedCrossRef

Yang JF, Tao HQ, Liu YM, Zhan XX, Liu Y, Wang XY, Wang JH, Mu LL, Yang LL, Gao ZM et al (2012) Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis (EAE) in mice. Clin Exp Immunol 170:254–265. doi:10.1111/j.1365-2249.2012.04661.x PubMedCentralPubMedCrossRef

Fitzgerald DC, Zhang G-X, El-Behi M, Fonseca-Kelly Z, Li H, Yu S, Saris CJM, Gran B, Ciric B, Rostami A (2007) Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 8:1372–1379. doi:10.1038/ni1540 PubMedCrossRef

Aloisi F, Ria F, Columba-Cabezas S, Hess H, Penna G, Adorini L (1999) Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation. Eur J Immunol 29:2705–2714. doi:10.1002/(SICI)1521-4141(199909)29:09<2705::AID-IMMU2705>3.0.CO;2-1 PubMedCrossRef

Sedgwick JD, Mössner R, Schwender S, ter Meulen V (1991) Major histocompatibility complex-expressing nonhematopoietic astroglial cells prime only CD8+ T lymphocytes: astroglial cells as perpetuators but not initiators of CD4+ T cell responses in the central nervous system. J Exp Med 173:1235–1246PubMedCrossRef

10.

Hindinger C, Bergmann CC, Hinton DR, Phares TW, Parra GI, Hussain S, Savarin C, Atkinson RD, Stohlman SA (2012) IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability. PLoS ONE 7, e42088. doi:10.1371/journal.pone.0042088 PubMedCentralPubMedCrossRef

11.

Waisman A, Hauptmann J, Regen T (2015) The role of IL-17 in CNS diseases. Acta Neuropathol 1–13. doi:10.1007/s00401-015-1402-7

12.

Rouvier E, Luciani MF, Mattéi MG, Denizot F, Golstein P (1993) CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus Saimiri gene. J Immunol 150:5445–5456PubMed

13.

Sarma Das J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, Fitzgerald DC, Shindler KS, Rostami A (2009) Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis. J Neuroinflammation 6:14. doi:10.1186/1742-2094-6-14 CrossRef

14.

Elain G, Jeanneau K, Rutkowska A, Mir AK, Dev KK (2014) The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes. Glia 62:725–735. doi:10.1002/glia.22637 PubMedCrossRef

15.

Yi H, Bai Y, Zhu X, Lin L, Zhao L, Wu X, Buch S, Wang L, Chao J, 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. doi:10.1007/s11481-014-9553-1 PubMedCrossRef

16.

Xiao Y, Jin J, Chang M, Nakaya M, Hu H, Zou Q, Zhou X, Brittain GC, Cheng X, Sun S-C (2014) TPL2 mediates autoimmune inflammation through activation of the TAK1 axis of IL-17 signaling. J Exp Med 211:1689–1702. doi:10.1084/jem.20132640 PubMedCentralPubMedCrossRef

17.

Meares GP, Ma X, Qin H, Benveniste EN (2012) Regulation of CCL20 expression in astrocytes by IL-6 and IL-17. Glia 60:771–781. doi:10.1002/glia.22307 PubMedCrossRef

18.

Liu G, Guo J, Liu J, Wang Z, Liang D (2014) Toll-like receptor signaling directly increases functional IL-17RA expression in neuroglial cells. Clin Immunol 154:127–140. doi:10.1016/j.clim.2014.07.006 PubMedCrossRef

19.

Kang Z, Altuntas CZ, Gulen MF, Liu C, Giltiay N, Qin H, Liu L, Qian W, Ransohoff RM, Bergmann C et al (2010) Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. Immunity 32:414–425. doi:10.1016/j.immuni.2010.03.004 PubMedCentralPubMedCrossRef

20.

Yan Y, Ding X, Li K, Ciric B, Wu S, Xu H, Gran B, Rostami A, Zhang G-X (2012) CNS-specific therapy for ongoing EAE by silencing IL-17 pathway in astrocytes. Mol Ther 20:1338–1348. doi:10.1038/mt.2012.12 PubMedCentralPubMedCrossRef

21.

Kang Z, Wang C, Zepp J, Wu L, Sun K, Zhao J, Chandrasekharan U, DiCorleto PE, Trapp BD, Ransohoff RM et al (2013) Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells. Nat Neurosci 16:1401–1408. doi:10.1038/nn.3505 PubMedCentralPubMedCrossRef

22.

Li X (2008) Act1 modulates autoimmunity through its dual functions in CD40L/BAFF and IL-17 signaling. Cytokine 41:105–113. doi:10.1016/j.cyto.2007.09.015 PubMedCrossRef

23.

Wu L, Zepp J, Li X (2012) Function of Act1 in IL-17 family signaling and autoimmunity. Adv Exp Med Biol 946:223–235. doi:10.1007/978-1-4614-0106-3_13 PubMedCrossRef

24.

Wang X, Deckert M, Xuan NT, Nishanth G, Just S, Waisman A, Naumann M, Schlüter D (2013) Astrocytic A20 ameliorates experimental autoimmune encephalomyelitis by inhibiting NF-κB- and STAT1-dependent chemokine production in astrocytes. Acta Neuropathol 126:711–724. doi:10.1007/s00401-013-1183-9 CrossRef

25.

Li Z, Li K, Zhu L, Kan Q, Yan Y, Kumar P, Xu H, Rostami A, Zhang G-X (2013) Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation. BMC Immunol 14:20. doi:10.1186/1471-2172-14-20 PubMedCentralPubMedCrossRef

26.

Heidary M, Rakhshi N, Pahlevan Kakhki M, Behmanesh M, Sanati MH, Sanadgol N, Kamaladini H, Nikravesh A (2014) The analysis of correlation between IL-1B gene expression and genotyping in multiple sclerosis patients. J Neurol Sci 343:41–45. doi:10.1016/j.jns.2014.05.013 PubMedCrossRef

27.

Wang Y, Jin S, Sonobe Y, Cheng Y, Horiuchi H, Parajuli B, Kawanokuchi J, Mizuno T, Takeuchi H, Suzumura A (2014) Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. PLoS ONE 9, e110024. doi:10.1371/journal.pone.0110024 PubMedCentralPubMedCrossRef

28.

Ambrosini E, Columba-Cabezas S, Serafini B, Muscella A, Aloisi F (2003) Astrocytes are the major intracerebral source of macrophage inflammatory protein-3alpha/CCL20 in relapsing experimental autoimmune encephalomyelitis and in vitro. Glia 41:290–300. doi:10.1002/glia.10193 PubMedCrossRef

29.

Argaw AT, Zhang Y, Snyder BJ, Zhao M-L, Kopp N, Lee SC, Raine CS, Brosnan CF, John GR (2006) IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J Immunol 177:5574–5584PubMedCrossRef

30.

Narcisse L, Scemes E, Zhao Y, Lee SC, Brosnan CF (2005) The cytokine IL-1beta transiently enhances P2X7 receptor expression and function in human astrocytes. Glia 49:245–258. doi:10.1002/glia.20110 PubMedCentralPubMedCrossRef

31.

Mehindate K, Sahlas DJ, Frankel D, Mawal Y, Liberman A, Corcos J, Dion S, Schipper HM (2001) Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis. J Neurochem 77:1386–1395PubMedCrossRef

32.

John GR, Chen L, Rivieccio MA, Melendez-Vasquez CV, Hartley A, Brosnan CF (2004) Interleukin-1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis. J Neurosci 24:2837–2845. doi:10.1523/JNEUROSCI.4789-03.2004 PubMedCrossRef

33.

Li R, Xu W, Chen Y, Qiu W, Shu Y, Wu A, Dai Y, Bao J, Lu Z, Hu X (2014) Raloxifene suppresses experimental autoimmune encephalomyelitis and NF-κB-dependent CCL20 expression in reactive astrocytes. PLoS ONE 9, e94320. doi:10.1371/journal.pone.0094320 PubMedCentralPubMedCrossRef

34.

Wu C, Leong SY, Moore CS, Cui Q-L, Gris P, Bernier L-P, Johnson TA, Séguéla P, Kennedy TE, Bar-Or A et al (2013) Dual effects of daily FTY720 on human astrocytes in vitro: relevance for neuroinflammation. J Neuroinflammation 10:41. doi:10.1186/1742-2094-10-41 PubMedCentralPubMedCrossRef

35.

Di Penta A, Chiba A, Alloza I, Wyssenbach A, Yamamura T, Villoslada P, Miyake S, Vandenbroeck K (2013) A trifluoromethyl analogue of celecoxib exerts beneficial effects in neuroinflammation. PLoS ONE 8, e83119. doi:10.1371/journal.pone.0083119 PubMedCentralPubMedCrossRef

36.

de Nunes AKS, Rapôso C, de Luna RLA, Cruz-Höfling MAD, Peixoto CA (2012) Sildenafil (Viagra®) down regulates cytokines and prevents demyelination in a cuprizone-induced MS mouse model. Cytokine 60:540–551. doi:10.1016/j.cyto.2012.06.011 PubMedCrossRef

37.

Wight RD, Tull CA, Deel MW, Stroope BL, Eubanks AG, Chavis JA, Drew PD, Hensley LL (2012) Resveratrol effects on astrocyte function: relevance to neurodegenerative diseases. Biochem Biophys Res Commun 426:112–115. doi:10.1016/j.bbrc.2012.08.045 PubMedCentralPubMedCrossRef

38.

Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD (2012) Mitoxantrone repression of astrocyte activation: relevance to multiple sclerosis. Brain Res 1473:236–241. doi:10.1016/j.brainres.2012.07.054 PubMedCentralPubMedCrossRef

39.

Wilms H, Sievers J, Rickert U, Rostami-Yazdi M, Mrowietz U, Lucius R (2010) Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. J Neuroinflammation 7:30. doi:10.1186/1742-2094-7-30 PubMedCentralPubMedCrossRef

40.

Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. doi:10.1146/annurev.immunol.021908.132612 PubMedCrossRef

41.

Fukaya T, Someya K, Hibino S, Okada M, Yamane H, Taniguchi K, Yoshimura A (2014) Loss of Sprouty4 in T cells ameliorates experimental autoimmune encephalomyelitis in mice by negatively regulating IL-1β receptor expression. Biochem Biophys Res Commun 447:471–478. doi:10.1016/j.bbrc.2014.04.012 PubMedCrossRef

42.

Hirsch JD, Gnanasakthy A, Lale R, Choi K, Sarkin AJ (2014) Efficacy of canakinumab vs. triamcinolone acetonide according to multiple gouty arthritis-related health outcomes measures. Int J Clin Pract 68:1503–1507. doi:10.1111/ijcp.12521 PubMedCrossRef

43.

Zager A, Peron JP, Mennecier G, Rodrigues SC, Aloia TP, Palermo-Neto J (2015) Maternal immune activation in late gestation increases neuroinflammation and aggravates experimental autoimmune encephalomyelitis in the offspring. Brain Behav Immun 43:159–171. doi:10.1016/j.bbi.2014.07.021 PubMedCrossRef

44.

Bajramović JJ, Bsibsi M, Geutskens SB, Hassankhan R, Verhulst KC, Stege GJ, de Groot CJ, van Noort JM (2000) Differential expression of stress proteins in human adult astrocytes in response to cytokines. J Neuroimmunol 106:14–22PubMedCrossRef

45.

Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A (1998) IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28:2178–2187. doi:10.1002/(SICI)1521-4141(199807)28:07<2178::AID-IMMU2178>3.0.CO;2-D PubMedCrossRef

46.

Giralt M, Ramos R, Quintana A, Ferrer B, Erta M, Castro-Freire M, Comes G, Sanz E, Unzeta M, Pifarré P et al (2013) Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. Glia 61:587–600. doi:10.1002/glia.22457 PubMedCrossRef

47.

Quintana A, Müller M, Frausto RF, Ramos R, Getts DR, Sanz E, Hofer MJ, Krauthausen M, King NJC, Hidalgo J et al (2009) Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. J Immunol 183:2079–2088. doi:10.4049/jimmunol.0900242 PubMedCrossRef

48.

Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L (1993) Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90:10061–10065PubMedCentralPubMedCrossRef

49.

Middeldorp J, Hol EM (2011) GFAP in health and disease. Prog Neurobiol 93:421–443. doi:10.1016/j.pneurobio.2011.01.005 PubMedCrossRef

50.

Haroon F, Drögemüller K, Händel U, Brunn A, Reinhold D, Nishanth G, Mueller W, Trautwein C, Ernst M, Deckert M et al (2011) Gp130-dependent astrocytic survival is critical for the control of autoimmune central nervous system inflammation. J Immunol 186:6521–6531. doi:10.4049/jimmunol.1001135 PubMedCrossRef

51.

Smith KJ, Lassmann H (2002) The role of nitric oxide in multiple sclerosis. Lancet Neurol 1:232–241PubMedCrossRef

52.

Liu JS, Zhao ML, Brosnan CF, Lee SC (2001) Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158:2057–2066. doi:10.1016/S0002-9440(10)64677-9 PubMedCentralPubMedCrossRef

53.

Hill KE, Zollinger LV, Watt HE, Carlson NG, Rose JW (2004) Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: distribution, cellular expression and association with myelin damage. J Neuroimmunol 151:171–179. doi:10.1016/j.jneuroim.2004.02.005 PubMedCrossRef

54.

Brenner T, Brocke S, Szafer F, Sobel RA, Parkinson JF, Perez DH, Steinman L (1997) Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J Immunol 158:2940–2946PubMed

55.

Petković F, Blaževski J, Momčilović M, Mostarica Stojkovic M, Miljković D (2013) Nitric oxide inhibits CXCL12 expression in neuroinflammation. Immunol Cell Biol 91:427–434. doi:10.1038/icb.2013.23 PubMedCrossRef

56.

Guthikonda P, Baker J, Mattson DH (1998) Interferon-beta-1-b (IFN-B) decreases induced nitric oxide (NO) production by a human astrocytoma cell line. J Neuroimmunol 82:133–139PubMedCrossRef

57.

Wingerchuk DM, Carter JL (2014) Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc 89:225–240. doi:10.1016/j.mayocp.2013.11.002 PubMedCrossRef

58.

Al-Izki S, Pryce G, Jackson SJ, Giovannoni G, Baker D (2011) Immunosuppression with FTY720 is insufficient to prevent secondary progressive neurodegeneration in experimental autoimmune encephalomyelitis. Mult Scler 17:939–948. doi:10.1177/1352458511400476 PubMedCrossRef

59.

Kleinewietfeld M, Hafler DA (2014) Regulatory T cells in autoimmune neuroinflammation. Immunol Rev 259:231–244. doi:10.1111/imr.12169 PubMedCentralPubMedCrossRef

60.

Bettini M, Vignali DAA (2009) Regulatory T cells and inhibitory cytokines in autoimmunity. Curr Opin Immunol 21:612–618. doi:10.1016/j.coi.2009.09.011 PubMedCentralPubMedCrossRef

61.

Heinemann C, Heink S, Petermann F, Vasanthakumar A, Rothhammer V, Doorduijn E, Mitsdoerffer M, Sie C, Prazeres da Costa O, Buch T et al (2014) IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1. Nat Commun 5:3770. doi:10.1038/ncomms4770 PubMedCrossRef

62.

Beebe AM, Cua DJ, de Waal Malefyt R (2002) The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev 13:403–412PubMedCrossRef

63.

Blaževski J, Petković F, Momčilović M, Jevtić B, Miljković D, Mostarica Stojkovic M (2013) High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis. Immunobiology 218:1192–1199. doi:10.1016/j.imbio.2013.04.004 PubMedCrossRef

64.

Molina-Holgado E, Arévalo-Martín A, Castrillo A, Boscá L, Vela JM, Guaza C (2002) Interleukin-4 and interleukin-10 modulate nuclear factor kappaB activity and nitric oxide synthase-2 expression in Theiler’s virus-infected brain astrocytes. J Neurochem 81:1242–1252PubMedCrossRef

65.

Molina-Holgado E, Arévalo-Martín A, Ortiz S, Vela JM, Guaza C (2002) Theiler’s virus infection induces the expression of cyclooxygenase-2 in murine astrocytes: inhibition by the anti-inflammatory cytokines interleukin-4 and interleukin-10. Neurosci Lett 324:237–241PubMedCrossRef

66.

Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R (2003) Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc Natl Acad Sci U S A 100:14157–14162. doi:10.1073/pnas.2336171100 PubMedCentralPubMedCrossRef

67.

Yang J, Jiang Z, Fitzgerald DC, Ma C, Yu S, Li H, Zhao Z, Li Y, Ciric B, Curtis M et al (2009) Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis. J Clin Invest 119:3678–3691. doi:10.1172/JCI37914 PubMedCentralPubMedCrossRef

68.

Mohsenzadegan M, Fayazi MR, Abdolmaleki M, Bakhshayesh M, Seif F, Mousavizadeh K (2015) Direct immunomodulatory influence of IFN-β on human astrocytoma cells. Immunopharmacol Immunotoxicol 37:214–219. doi:10.3109/08923973.2015.1014559 PubMedCrossRef

69.

Bsibsi M, Persoon-Deen C, Verwer RWH, Meeuwsen S, Ravid R, van Noort JM (2006) Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia 53:688–695. doi:10.1002/glia.20328 PubMedCrossRef

70.

Li X-L, Lv J, Xi N-N, Wang T, Shang X-F, Xu H-Q, Han Z, O’Byrne KT, Li X-F, Zheng R-Y (2010) Neonatal endotoxin exposure suppresses experimental autoimmune encephalomyelitis through regulating the immune cells responsivity in the central nervous system of adult rats. Biochem Biophys Res Commun 398:302–308. doi:10.1016/j.bbrc.2010.06.086 PubMedCrossRef

71.

Cannella B, Raine CS (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 37:424–435. doi:10.1002/ana.410370404 PubMedCrossRef

72.

Cannella B, Raine CS (2004) Multiple sclerosis: cytokine receptors on oligodendrocytes predict innate regulation. Ann Neurol 55:46–57. doi:10.1002/ana.10764 PubMedCrossRef

73.

Hulshof S, Montagne L, De Groot CJA, Van Der Valk P (2002) Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions. Glia 38:24–35. doi:10.1002/glia.10050 PubMedCrossRef

74.

Cheng W, Chen G (2014) Chemokines and chemokine receptors in multiple sclerosis. Mediat Inflamm 2014:659206–659208. doi:10.1155/2014/659206

75.

Yoshimura T, Robinson EA, Tanaka S, Appella E, Kuratsu J, Leonard EJ (1989) Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. J Exp Med 169:1449–1459PubMedCrossRef

76.

Yoshimura T, Yuhki N, Moore SK, Appella E, Lerman MI, Leonard EJ (1989) Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett 244:487–493PubMedCrossRef

77.

O Connor T, Borsig L, Heikenwalder M (2015) CCL2-CCR2 signaling in disease pathogenesis. Endocr Metab Immune Disord Drug Targets

78.

Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Tuohy VK (1993) Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB J 7:592–600PubMed

79.

Adamus G, Machnicki M, Amundson D, Adlard K, Offner H (1997) Similar pattern of MCP-1 expression in spinal cords and eyes of Lewis rats with experimental autoimmune encephalomyelitis associated anterior uveitis. J Neurosci Res 50:531–538. doi:10.1002/(SICI)1097-4547(19971115)50:4<531::AID-JNR4>3.0.CO;2-F PubMedCrossRef

80.

Shrestha B, Ge S, Pachter JS (2014) Resolution of central nervous system astrocytic and endothelial sources of CCL2 gene expression during evolving neuroinflammation. Fluids Barriers CNS 11:6. doi:10.1186/2045-8118-11-6 PubMedCentralPubMedCrossRef

81.

Mayo L, Trauger SA, Blain M, Nadeau M, Patel BN, Alvarez JI, Mascanfroni ID, Yeste A, Kivisakk P, Kallas K et al (2014) Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med. doi:10.1038/nm.3681 PubMedCentralPubMed

82.

Hayashi M, Luo Y, Laning J, Strieter RM, Dorf ME (1995) Production and function of monocyte chemoattractant protein-1 and other beta-chemokines in murine glial cells. J Neuroimmunol 60:143–150PubMedCrossRef

83.

Glabinski AR, Krakowski M, Han Y, Owens T, Ransohoff RM (1999) Chemokine expression in GKO mice (lacking interferon-gamma) with experimental autoimmune encephalomyelitis. J Neurovirol 5:95–101PubMedCrossRef

84.

Giraud SN, Caron CM, Pham-Dinh D, Kitabgi P, Nicot AB (2010) Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression in reactive astrocytes. Proc Natl Acad Sci 107:8416–8421. doi:10.1073/pnas.0910627107 PubMedCentralPubMedCrossRef

85.

Kim RY, Hoffman AS, Itoh N, Ao Y, Spence R, Sofroniew MV, Voskuhl RR (2014) Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 274:53–61. doi:10.1016/j.jneuroim.2014.06.009 PubMedCentralPubMedCrossRef

86.

Paul D, Ge S, Lemire Y, Jellison ER, Serwanski DR, Ruddle NH, 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. doi:10.1186/1742-2094-11-10 PubMedCentralPubMedCrossRef

87.

Moreno M, Bannerman P, Ma J, Guo F, Miers L, Soulika AM, 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. doi:10.1523/JNEUROSCI.1137-14.2014 PubMedCentralPubMedCrossRef

88.

Quinones MP, Kalkonde Y, Estrada CA, Jimenez F, Ramirez R, Mahimainathan L, Mummidi S, Choudhury GG, Martinez H, Adams L et al (2008) Role of astrocytes and chemokine systems in acute TNFalpha induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-kappaB and Akt. Mol Cell Neurosci 37:96–109. doi:10.1016/j.mcn.2007.08.017 PubMedCentralPubMedCrossRef

89.

Brouwer N, Zuurman MW, Wei T, Ransohoff RM, Boddeke HWGM, Biber K (2004) Induction of glial L-CCR mRNA expression in spinal cord and brain in experimental autoimmune encephalomyelitis. Glia 46:84–94. doi:10.1002/glia.10352 PubMedCrossRef

90.

Zuurman MW, Heeroma J, Brouwer N, Boddeke HWGM, Biber K (2003) LPS-induced expression of a novel chemokine receptor (L-CCR) in mouse glial cells in vitro and in vivo. Glia 41:327–336. doi:10.1002/glia.10156 PubMedCrossRef

91.

Biber K, Zuurman MW, Homan H, Boddeke HWGM (2003) Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8. J Leukoc Biol 74:243–251PubMedCrossRef

92.

Ge S, Shrestha B, Paul D, Keating C, Cone R, Guglielmotti A, Pachter JS (2012) The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis. J Neuroinflammation 9:171. doi:10.1186/1742-2094-9-171 PubMedCentralPubMedCrossRef

93.

Guo M-F, Meng J, Li Y-H, Yu J-Z, Liu C-Y, Feng L, Yang W-F, Li J-L, Feng Q-J, Xiao B-G et al (2014) The inhibition of Rho kinase blocks cell migration and accumulation possibly by challenging inflammatory cytokines and chemokines on astrocytes. J Neurol Sci 343:69–75. doi:10.1016/j.jns.2014.05.034 PubMedCrossRef

94.

Spence RD, Wisdom AJ, Cao Y, Hill HM, Mongerson CRL, Stapornkul B, Itoh N, Sofroniew MV, Voskuhl RR (2013) Estrogen mediates neuroprotection and anti-inflammatory effects during EAE through ERα signaling on astrocytes but not through ERβ signaling on astrocytes or neurons. J Neurosci 33:10924–10933. doi:10.1523/JNEUROSCI.0886-13.2013 PubMedCentralPubMedCrossRef

95.

Utans-Schneitz U, Lorez H, Klinkert WE, da Silva J, Lesslauer W (1998) A novel rat CC chemokine, identified by targeted differential display, is upregulated in brain inflammation. J Neuroimmunol 92:179–190PubMedCrossRef

96.

Varona R, Zaballos A, Gutiérrez J, Martín P, Roncal F, Albar JP, Ardavín C, Márquez G (1998) Molecular cloning, functional characterization and mRNA expression analysis of the murine chemokine receptor CCR6 and its specific ligand MIP-3alpha. FEBS Lett 440:188–194PubMedCrossRef

97.

Farina C, Krumbholz M, Giese T, Hartmann G, Aloisi F, Meinl E (2005) Preferential expression and function of Toll-like receptor 3 in human astrocytes. J Neuroimmunol 159:12–19. doi:10.1016/j.jneuroim.2004.09.009 PubMedCrossRef

98.

Zhou Y, Sonobe Y, Akahori T, Jin S, Kawanokuchi J, Noda M, Iwakura Y, Mizuno T, Suzumura A (2011) IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes. J Immunol 186:4415–4421. doi:10.4049/jimmunol.1003307 PubMedCrossRef

99.

Liu X, Tian Y, Lu N, Gin T, Cheng CHK, Chan MTV (2013) Stat3 inhibition attenuates mechanical allodynia through transcriptional regulation of chemokine expression in spinal astrocytes. PLoS ONE 8, e75804. doi:10.1371/journal.pone.0075804 PubMedCentralPubMedCrossRef

100.

Reboldi A, Reboldi A, Coisne C, Coisne C, Baumjohann D, Baumjohann D, Benvenuto F, Benvenuto F, Bottinelli D, Bottinelli D et al (2009) C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10:514–523. doi:10.1038/ni.1716 PubMedCrossRef

101.

van Heteren JT, Rozenberg F, Aronica E, Troost D, Lebon P, Kuijpers TW (2008) Astrocytes produce interferon-alpha and CXCL10, but not IL-6 or CXCL8, in Aicardi-Goutières syndrome. Glia 56:568–578. doi:10.1002/glia.20639 PubMedCrossRef

102.

Uddin J, Garcia HH, Gilman RH, Gonzalez AE, Friedland JS (2005) Monocyte-astrocyte networks and the regulation of chemokine secretion in neurocysticercosis. J Immunol 175:3273–3281PubMedCrossRef

103.

Zheng JC, Huang Y, Tang K, Cui M, Niemann D, Lopez A, Morgello S, Chen S (2008) HIV-1-infected and/or immune-activated macrophages regulate astrocyte CXCL8 production through IL-1beta and TNF-alpha: involvement of mitogen-activated protein kinases and protein kinase R. J Neuroimmunol 200:100–110. doi:10.1016/j.jneuroim.2008.06.015 PubMedCentralPubMedCrossRef

104.

Subileau EA, Rezaie P, Davies HA, Colyer FM, Greenwood J, Male DK, Romero IA (2009) Expression of chemokines and their receptors by human brain endothelium: implications for multiple sclerosis. J Neuropathol Exp Neurol 68:227–240. doi:10.1097/NEN.0b013e318197eca7 PubMedCrossRef

105.

Choi SS, Lee HJ, Lim I, Satoh J-I, Kim SU (2014) Human astrocytes: secretome profiles of cytokines and chemokines. PLoS ONE 9, e92325. doi:10.1371/journal.pone.0092325 PubMedCentralPubMedCrossRef

106.

Meeuwsen S, Persoon-Deen C, Bsibsi M, Ravid R, van Noort JM (2003) Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli. Glia 43:243–253. doi:10.1002/glia.10259 PubMedCrossRef

107.

Jing T, Wu L, Borgmann K, Surendran S, Ghorpade A, Liu J, Xiong H (2010) Soluble factors from IL-1β-stimulated astrocytes activate NR1a/NR2B receptors: implications for HIV-1-induced neurodegeneration. Biochem Biophys Res Commun 402:241–246. doi:10.1016/j.bbrc.2010.10.006 PubMedCentralPubMedCrossRef

108.

Omari KM, John GR, Sealfon SC, Raine CS (2005) CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis. Brain 128:1003–1015. doi:10.1093/brain/awh479 PubMedCrossRef

109.

So EY, Kang MH, Kim BS (2006) Induction of chemokine and cytokine genes in astrocytes following infection with Theiler’s murine encephalomyelitis virus is mediated by the Toll-like receptor 3. Glia 53:858–867. doi:10.1002/glia.20346 PubMedCrossRef

110.

Mohan H, Friese A, Albrecht S, Krumbholz M, Elliott CL, Arthur A, Menon R, Farina C, Junker A, Stadelmann C et al (2014) Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination. Acta Neuropathol Commun 2:178. doi:10.1186/s40478-014-0168-9

111.

Kelland EE, Gilmore W, Weiner LP, Lund BT (2011) The dual role of CXCL8 in human CNS stem cell function: multipotent neural stem cell death and oligodendrocyte progenitor cell chemotaxis. Glia 59:1864–1878. doi:10.1002/glia.21230 PubMedCrossRef

112.

Khalifa KA, Radwan WM, Attallah KM, Hosney H, Eed EM (2014) Pretreatment serum interferon gamma inducible protein-10 as biomarker of fibrosis and predictor of virological response in genotype 4 hepatitis C virus infection. Acta Gastroenterol Belg 77:401–407PubMed

113.

Vazirinejad R, Ahmadi Z, Kazemi Arababadi M, Hassanshahi G, Kennedy D (2014) The biological functions, structure and sources of CXCL10 and its outstanding part in the pathophysiology of multiple sclerosis. Neuroimmunomodulation 21:322–330. doi:10.1159/000357780 PubMedCrossRef

114.

Carter SL, Müller M, Manders PM, Campbell IL (2007) Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro. Glia 55:1728–1739. doi:10.1002/glia.20587 PubMedCrossRef

115.

Millward JM, Caruso M, Campbell IL, Gauldie J, Owens T (2007) IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell entry to the central nervous system. J Immunol 178:8175–8182PubMedCrossRef

116.

Glabinski AR, Tani M, Tuohy VK, Tuthill RJ, Ransohoff RM (1995) Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis. Brain Behav Immun 9:315–330. doi:10.1006/brbi.1995.1030 PubMedCrossRef

117.

Rubio N, Arevalo M-A, Cerciat M, Sanz-Rodriguez F, Unkila M, Garcia-Segura LM (2014) Theiler’s virus infection provokes the overexpression of genes coding for the chemokine Ip10 (CXCL10) in SJL/J murine astrocytes, which can be inhibited by modulators of estrogen receptors. J Neurovirol 20:485–495. doi:10.1007/s13365-014-0273-3 PubMedCrossRef

118.

Imaizumi T, Numata A, Yano C, Yoshida H, Meng P, Hayakari R, Xing F, Wang L, Matsumiya T, Tanji K et al (2014) ISG54 and ISG56 are induced by TLR3 signaling in U373MG human astrocytoma cells: possible involvement in CXCL10 expression. Neurosci Res 84:34–42. doi:10.1016/j.neures.2014.03.001 PubMedCrossRef

119.

Imaizumi T, Murakami K, Ohta K, Seki H, Matsumiya T, Meng P, Hayakari R, Xing F, Aizawa-Yashiro T, Tatsuta T et al (2013) MDA5 and ISG56 mediate CXCL10 expression induced by toll-like receptor 4 activation in U373MG human astrocytoma cells. Neurosci Res 76:195–206. doi:10.1016/j.neures.2013.05.002 PubMedCrossRef

120.

Tanuma N, Sakuma H, Sasaki A, Matsumoto Y (2006) Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. Acta Neuropathol 112:195–204. doi:10.1007/s00401-006-0083-7 PubMedCrossRef

121.

Phares TW, Stohlman SA, Hinton DR, Bergmann CC (2013) Astrocyte-derived CXCL10 drives accumulation of antibody-secreting cells in the central nervous system during viral encephalomyelitis. J Virol 87:3382–3392. doi:10.1128/JVI.03307-12 PubMedCentralPubMedCrossRef

122.

Mills Ko E, Ma JH, Guo F, Miers L, Lee E, Bannerman P, Burns T, Ko D, Sohn J, Soulika AM et al (2014) Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model. J Neuroinflammation 11:105. doi:10.1186/1742-2094-11-105 PubMedCentralPubMedCrossRef

123.

Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgärtner W, Stangel M (2013) Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 136:147–167. doi:10.1093/brain/aws262 PubMedCrossRef

124.

Clarner T, Janssen K, Nellessen L, Stangel M, Skripuletz T, Krauspe B, Hess F-M, Denecke B, Beutner C, Linnartz-Gerlach B, et al. (2015) CXCL10 triggers early microglial activation in the cuprizone model. J Immunol 1401459. doi:10.4049/jimmunol.1401459

125.

Moore CS, Cui Q-L, Warsi NM, Durafourt BA, Zorko N, Owen DR, Antel JP, Bar-Or A (2015) Direct and indirect effects of immune and central nervous system-resident cells on human oligodendrocyte progenitor cell differentiation. J Immunol 194:761–772. doi:10.4049/jimmunol.1401156 PubMedCrossRef

126.

Sørensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM et al (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103:807–815. doi:10.1172/JCI5150 PubMedCentralPubMedCrossRef

127.

Sørensen TL, Trebst C, Kivisakk P, Klaege KL, Majmudar A, Ravid R, Lassmann H, Olsen DB, Strieter RM, Ransohoff RM et al (2002) Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system. J Neuroimmunol 127:59–68PubMedCrossRef

128.

Li M, Ransohoff RM (2008) Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 84:116–131. doi:10.1016/j.pneurobio.2007.11.003 PubMedCentralPubMedCrossRef

129.

Momčilović M, Mostarica Stojkovic M, Miljković D (2012) CXCL12 in control of neuroinflammation. Immunol Res 52:53–63. doi:10.1007/s12026-012-8282-x PubMedCrossRef

130.

McCandless EE, Wang Q, Woerner BM, Harper JM, Klein RS (2006) CXCL12 limits inflammation by localizing mononuclear infiltrates to the perivascular space during experimental autoimmune encephalomyelitis. J Immunol 177:8053–8064PubMedCrossRef

131.

Blaževski J, Petković F, Momčilović M, Jevtić B, Stojković MM, Miljković D (2015) Tumor necrosis factor stimulates expression of CXCL12 in astrocytes. Immunobiology. doi:10.1016/j.imbio.2015.01.007 PubMed

132.

Timotijević G, Petković F, Blaževski J, Momčilović M, Mostarica Stojkovic M, Miljković D (2013) CXCL12-γ expression is inhibited in neuroinflammation. Brain Res 1519:120–126. doi:10.1016/j.brainres.2013.04.056 PubMedCrossRef

133.

Meiron M, Zohar Y, Anunu R, Wildbaum G, Karin N (2008) CXCL12 (SDF-1alpha) suppresses ongoing experimental autoimmune encephalomyelitis by selecting antigen-specific regulatory T cells. J Exp Med 205:2643–2655. doi:10.1084/jem.20080730 PubMedCentralPubMedCrossRef

134.

Bezzi P, Domercq M, Brambilla L, Galli R, Schols D, De Clercq E, Vescovi A, Bagetta G, Kollias G, Meldolesi J et al (2001) CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci 4:702–710. doi:10.1038/89490 PubMedCrossRef

135.

Calderon TM, Eugenin EA, Lopez L, Kumar SS, Hesselgesser J, Raine CS, Berman JW (2006) A role for CXCL12 (SDF-1alpha) in the pathogenesis of multiple sclerosis: regulation of CXCL12 expression in astrocytes by soluble myelin basic protein. J Neuroimmunol 177:27–39. doi:10.1016/j.jneuroim.2006.05.003 PubMedCrossRef

Titel: Control of autoimmune CNS inflammation by astrocytes
verfasst von: Veit Rothhammer
Francisco J. Quintana
Publikationsdatum: 01.11.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Seminars in Immunopathology / Ausgabe 6/2015
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-015-0515-3

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