Abstract
microRNAs play a fundamental role in the immune system. One particular microRNA, miR-155 plays a critical role in hematopoietic cell development and tightly regulates innate and adaptive immune responses in response to infection. However, its dysregulation, more specifically its overexpression, is closely associated with various inflammatory disorders. The purpose of this review is to consolidate how miR-155 underpins a variety of processes that contribute to the pathology of multiple sclerosis (MS). In particular, the impact of miR-155 is discussed with respect to human pathology and animal models. How miR-155 contributes to the activation of pathogenic immune cells, the permeability of the blood-brain barrier, and neurodegeneration in relation to MS is described. Many environmental risk factors associated with MS susceptibility can cause upregulation of miR-155, while many of the current disease-modifying treatments may work by inhibiting miR-155. From this review, it is clear that miR-155 is a realistic and feasible diagnostic, prognostic, and therapeutic target for the treatment of MS.
References
Albrecht P, Bouchachia I, Goebels N, Henke N, Hofstetter HH et al (2012) Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation 9:163
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S et al (2016) Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med 8:1162–1183
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I (2015) Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol 14:263–273
Benedek G, Meza-Romero R, Jordan K, Keenlyside L, Offner H et al (2015) HLA-DRalpha1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection. J Neuroinflammation 12:123
Bruning U, Cerone L, Neufeld Z, Fitzpatrick SF, Cheong A et al (2011) MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol 31:4087–4096
Bruns H, Bottcher M, Qorraj M, Fabri M, Jitschin S et al (2017) CLL-cell-mediated MDSC induction by exosomal miR-155 transfer is disrupted by vitamin D. Leukemia 31:985–988
Butovsky O, Jedrychowski MP, Cialic R, Krasemann S, Murugaiyan G et al (2015) Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Ann Neurol 77:75–99
Cardoso AL, Guedes JR, Pereira de Almeida L, Pedroso de Lima MC (2012) miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production. Immunology 135:73–88
Cerutti C, Soblechero-Martin P, Wu D, Lopez-Ramirez MA, de Vries H et al (2016) MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro. Fluids Barriers CNS 13:8
Chekulaeva M, Filipowicz W (2009) Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 21:452–460
Chen Y, Liu W, Sun T, Huang Y, Wang Y et al (2013) 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. J Immunol 190:3687–3695
Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK et al (2011) MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol 8:467–477
Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S et al (2006) Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A 103:7024–7029
Cox MB, Cairns MJ, Gandhi KS, Carroll AP, Moscovis S et al (2010) MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 5:e12132
Cross AH, Naismith RT (2014) Established and novel disease-modifying treatments in multiple sclerosis. J Int Med 275(4):350–363. doi:10.1111/joim.12203. Epub 2014 March 11. Review. PubMed PMID:24444048
Cua DJ, Groux H, Hinton DR, Stohlman SA, Coffman RL (1999) Transgenic interleukin 10 prevents induction of experimental autoimmune encephalomyelitis. J Exp Med 189:1005–1010
Cua DJ, Hutchins B, LaFace DM, Stohlman SA, Coffman RL (2001) Central nervous system expression of IL-10 inhibits autoimmune encephalomyelitis. J Immunol 166:602–608
Dargahi N, Katsara M, Tselios T, Androutsou ME, de Courten M et al (2017) Multiple sclerosis: immunopathology and treatment update. Brain Sci 7
Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15:545–558
Eis PS, Tam W, Sun L, Chadburn A, Li Z et al (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A 102:3627–3632
Escobar TM, Kanellopoulou C, Kugler DG, Kilaru G, Nguyen CK et al (2014) miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression. Immunity 40:865–879
Faravelli I, Corti S (2017) MicroRNA-directed neuronal reprogramming as a therapeutic strategy for neurological diseases. Mol Neurobiol
Freilich RW, Woodbury ME, Ikezu T (2013) Integrated expression profiles of mRNA and miRNA in polarized primary murine microglia. PLoS One 8:e79416
Galloway DA, Moore CS (2016) miRNAs as emerging regulators of oligodendrocyte development and differentiation. Front cell. Dev Biol 4:59
Gandhi R (2015) miRNA in multiple sclerosis: search for novel biomarkers. Mult Scler 21:1095–1103
Gantier MP, McCoy CE, Rusinova I, Saulep D, Wang D et al (2011) Analysis of microRNA turnover in mammalian cells following Dicer1 ablation. Nucleic Acids Res 39:5692–5703
Gao L, Ai J, Xie Z, Zhou C, Liu C et al (2015) Dynamic expression of viral and cellular microRNAs in infectious mononucleosis caused by primary Epstein-Barr virus infection in children. Virol J 12:208
Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, et al. (2008) Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB
Goverman J (2009) Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9:393–407
Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, et al. (2007) Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet
Guedes JR, Custodia CM, Silva RJ, de Almeida LP, Pedroso de Lima MC et al (2014) Early miR-155 upregulation contributes to neuroinflammation in Alzheimer’s disease triple transgenic mouse model. Hum Mol Genet 23:6286–6301
Guinn D, Ruppert AS, Maddocks K, Jaglowski S, Gordon A et al (2015) miR-155 expression is associated with chemoimmunotherapy outcome and is modulated by Bruton’s tyrosine kinase inhibition with Ibrutinib. Leukemia 29:1210–1213
Hartmann FJ, Khademi M, Aram J, Ammann S, Kockum I et al (2014) Multiple sclerosis-associated IL2RA polymorphism controls GM-CSF production in human TH cells. Nat Commun 5:5056
Hecker M, Thamilarasan M, Koczan D, Schroder I, Flechtner K et al (2013) MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci 14:16087–16110
Hu R, Huffaker TB, Kagele DA, Runtsch MC, Bake E et al (2013) MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression. J Immunol 190:5972–5980
Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD (1990) Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med 172:1025–1033
International Multiple Sclerosis Genetics C, Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, et al (2013) Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45:1353–1360
Iosue I, Quaranta R, Masciarelli S, Fontemaggi G, Batassa EM et al (2013) Argonaute 2 sustains the gene expression program driving human monocytic differentiation of acute myeloid leukemia cells. Cell Death Dis 4:e926
Jablonski KA, Gaudet AD, Amici SA, Popovich PG, Guerau-de-Arellano M (2016) Control of the inflammatory macrophage transcriptional signature by miR-155. PLoS One 11:e0159724
Jagot F, Davoust N (2016) Is it worth considering circulating microRNAs in multiple sclerosis? Front Immunol 7:129
Jevtic B, Timotijevic G, Stanisavljevic S, Momcilovic M, Mostarica Stojkovic M et al (2015) Micro RNA-155 participates in re-activation of encephalitogenic T cells. Biomed Pharmacother 74:206–210
Jiang Z, Jiang JX, Zhang GX (2014) Macrophages: a double-edged sword in experimental autoimmune encephalomyelitis. Immunol Lett 160:17–22
Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F et al (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132:3342–3352
Karkeni E, Bonnet L, Marcotorchino J, Tourniaire F, Astier J, et al. (2017) Vitamin D limits inflammation-linked microRNA expression in adipocytes in vitro and in vivo: A new mechanism for the regulation of inflammation by vitamin D. Epigenetics:0
Keller A, Leidinger P, Lange J, Borries A, Schroers H et al (2009) Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One 4:e7440
Keller A, Leidinger P, Steinmeyer F, Stähler C, Franke A, Hemmrich-Stanisak G, Kappel A, Wright I, Dörr J, Paul F, Diem R, Tocariu-Krick B, Meder B, Backes C, Meese E, Ruprecht K (2014) Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler 20(3):295–303. doi:10.1177/1352458513496343. Epub 2013 Jul 8. PubMed PMID:23836875
Keller A, Leidinger P, Steinmeyer F, Stahler C, Franke A et al (2014) Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler 20:295–303
Kelly B, O’Neill LA (2015) Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res 25:771–784
Kin K, Miyagawa S, Fukushima S, Shirakawa Y, Torikai K et al (2012) Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm. J Am Heart Assoc 1:e000745
Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, Kroesen BJ, van den Berg A (2005) BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 207(2):243–249. PubMed PMID:16041695
Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414
Lashine YA, Salah S, Aboelenein HR, Abdelaziz AI (2015) Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients. Lupus 24(3):240–247. doi:10.1177/0961203314552117. Epub 2014 September 24. PubMed PMID:25253569
Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13:622–638
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–487
Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA, Cullen BR (2010) Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J Virol 84:11670–11678
Liu G, Abraham E (2013) MicroRNAs in immune response and macrophage polarization. Arterioscler Thromb Vasc Biol 33:170–177
Lopez-Ramirez MA, Wu D, Pryce G, Simpson JE, Reijerkerk A et al (2014) MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. FASEB J 28:2551–2565
Louafi F, Martinez-Nunez RT, Sanchez-Elsner T (2010) MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}. J Biol Chem 285:41328–41336
Lu C, Huang X, Zhang X, Roensch K, Cao Q et al (2011) miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. Blood 117:4293–4303
Lu F, Weidmer A, Liu CG, Volinia S, Croce CM et al (2008) Epstein-Barr virus-induced miR-155 attenuates NF-kappaB signaling and stabilizes latent virus persistence. J Virol 82:10436–10443
Lund C, Nakken KO, Edland A, Celius EG (2014) Multiple sclerosis and seizures: incidence and prevalence over 40 years. Acta Neurol Scand 130:368–373
Mameli G, Arru G, Caggiu E, Niegowska M, Leoni S et al (2016) Natalizumab therapy modulates miR-155, miR-26a and Proinflammatory cytokine expression in MS patients. PLoS One 11:e0157153
Mancardi G, Saccardi R (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7:626–636
Martinelli-Boneschi F, Fenoglio C, Brambilla P, Sorosina M, Giacalone G et al (2012) MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers. Neurosci Lett 508:4–8
Martinez-Nunez RT, Louafi F, Sanchez-Elsner T (2011) The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1). J Biol Chem 286:1786–1794
McCoy CE, Sheedy FJ, Qualls JE, Doyle SL, Quinn SR et al (2010) IL-10 inhibits miR-155 induction by toll-like receptors. J Biol Chem 285:20492–20498
Michell-Robinson MA, Moore CS, Healy LM, Osso LA, Zorko N et al (2016) Effects of fumarates on circulating and CNS myeloid cells in multiple sclerosis. Ann Clin Transl Neurol 3:27–41
Minagar A, Alexander JS (2003) Blood-brain barrier disruption in multiple sclerosis. Mult Scler 9:540–549
Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM et al (2013) M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 16:1211–1218
Moore CS, Rao VT, Durafourt BA, Bedell BJ, Ludwin SK, Bar-Or A, Antel JP (2013) miR-155 as a multiple sclerosisrelevant regulator of myeloid cell polarization. Ann Neurol 74(5):709–720. doi:10.1002/ana.23967. Epub 2013 September 23. PubMed PMID: 23818336
Moutsianas L, Jostins L, Beecham AH, Dilthey AT, Xifara DK et al (2015) Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat Genet 47:1107–1113
Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL (2011) Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol 187:2213–2221
Mycko MP, Cichalewska M, Cwiklinska H, Selmaj KW (2015) miR-155-3p drives the development of autoimmune demyelination by regulation of heat shock protein 40. J Neurosci 35:16504–16515
Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M et al (2011) A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 17:495–499
Noorbakhsh F, Ellestad KK, Maingat F, Warren KG, Han MH et al (2011) Impaired neurosteroid synthesis in multiple sclerosis. Brain 134:2703–2721
O’Connell RM, Chaudhuri AA, Rao DS, Baltimore D (2009) Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A 106:7113–7118
O’Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL et al (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33:607–619
O’Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312
O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D (2010) Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 10:111–122
O’Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD et al (2008) Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 205:585–594
O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104:1604–1609
O’Neill LA, Sheedy FJ, McCoy CE (2011) MicroRNAs: the fine-tuners of toll-like receptor signalling. Nat Rev Immunol 11:163–175
Otaegui D, Baranzini SE, Armananzas R, Calvo B, Munoz-Culla M et al (2009) Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One 4:e6309
Paraboschi EM, Solda G, Gemmati D, Orioli E, Zeri G et al (2011) Genetic association and altered gene expression of mir-155 in multiple sclerosis patients. Int J Mol Sci 12:8695–8712
Payne NL, Sun G, McDonald C, Moussa L, Emerson-Webber A et al (2013) Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity. Brain Behav Immun 30:103–114
Pedersen AW, Holmstrom K, Jensen SS, Fuchs D, Rasmussen S et al (2009) Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells. Clin Exp Immunol 157:48–59
Pena-Philippides JC, Caballero-Garrido E, Lordkipanidze T, Roitbak T (2016) In vivo inhibition of miR-155 significantly alters post-stroke inflammatory response. J Neuroinflammation 13:287
Pender MP, Burrows SR (2014) Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clin Transl Immunol 3:e27
Ponomarev ED, Veremeyko T, Weiner HL (2013) MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS. Glia 61:91–103
Pugliatti M, Rosati G, Carton H, Riise T, Drulovic J et al (2006) The epidemiology of multiple sclerosis in Europe. Eur J Neurol 13:700–722
Pulkkinen KH, Yla-Herttuala S, Levonen AL (2011) Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells. Free Radic Biol Med 51:2124–2131
Quinn SR, Mangan NE, Caffrey BE, Gantier MP, Williams BR et al (2014) The role of Ets2 transcription factor in the induction of microRNA-155 (miR-155) by lipopolysaccharide and its targeting by interleukin-10. J Biol Chem 289:4316–4325
Rahadiani N, Takakuwa T, Tresnasari K, Morii E, Aozasa K (2008) Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell lines. Biochem Biophys Res Commun 377:579–583
Rawji KS, Yong VW (2013) The benefits and detriments of macrophages/microglia in models of multiple sclerosis. Clin Dev Immunol 2013:948976
Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316(5824):608–611. PubMed PMID:17463290; PubMed Central PMCID:PMC2610435
Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG et al (2009) A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proc Natl Acad Sci U S A 106:17475–17480
Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203–222
Samoilova EB, Horton JL, Chen Y (1998) Acceleration of experimental autoimmune encephalomyelitis in interleukin-10-deficient mice: roles of interleukin-10 in disease progression and recovery. Cell Immunol 188:118–124
Sanders KA, Benton MC, Lea RA, Maltby VE, Agland S et al (2016) Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells. Clin Epigenetics 8:87
Schmidt C (2016) Biology: a degenerative affliction. Nature 540:S2–S3
Seddiki N, Brezar V, Ruffin N, Levy Y, Swaminathan S (2014) Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology 142:32–38
Seeger FH, Zeiher AM, Dimmeler S (2013) MicroRNAs in stem cell function and regenerative therapy of the heart. Arterioscler Thromb Vasc Biol 33:1739–1746
Singh J, Deshpande M, Suhail H, Rattan R, Giri S (2016) Targeted stage-specific inflammatory microRNA profiling in urine during disease progression in experimental autoimmune encephalomyelitis: markers of disease progression and drug response. J Neuroimmune Pharmacol 11:84–97
Skalsky RL, Corcoran DL, Gottwein E, Frank CL, Kang D et al (2012) The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog 8:e1002484
So AY, Garcia-Flores Y, Minisandram A, Martin A, Taganov K et al (2012) Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice. Blood 120:2428–2437
Sondergaard HB, Hesse D, Krakauer M, Sorensen PS, Sellebjerg F (2013) Differential microRNA expression in blood in multiple sclerosis. Mult Scler 19:1849–1857
Sun HX, Zeng DY, Li RT, Pang RP, Yang H et al (2012) Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension 60:1407–1414
Tannahill GM, Iraci N, Gaude E, Frezza C, Pluchino S (2015) Metabolic reprograming of mononuclear phagocytes in progressive multiple sclerosis. Front Immunol 6:106
Tarassishin L, Loudig O, Bauman A, Shafit-Zagardo B, Suh HS et al (2011) Interferon regulatory factor 3 inhibits astrocyte inflammatory gene expression through suppression of the proinflammatory miR-155 and miR-155*. Glia 59:1911–1922
Teng G, Hakimpour P, Landgraf P, Rice A, Tuschl T et al (2008) MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28:621–629
Thai TH, Calado DP, Casola S, Ansel KM, Xiao C et al (2007) Regulation of the germinal center response by microRNA-155. Science 316:604–608
Thome AD, Harms AS, Volpicelli-Daley LA, Standaert DG (2016) microRNA-155 regulates alpha-Synuclein-induced inflammatory responses in models of Parkinson disease. J Neurosci 36:2383–2390
Tran EH, Hoekstra K, van Rooijen N, Dijkstra CD, Owens T (1998) Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J Immunol 161:3767–3775
Tsitsiou E, Lindsay MA (2009) microRNAs and the immune response. Curr Opin Pharmacol 9:514–520
Vaknin I, Kunis G, Miller O, Butovsky O, Bukshpan S et al (2011) Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis. PLoS One 6:e26921
van den Berg A, Kroesen BJ, Kooistra K, de Jong D, Briggs J et al (2003) High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer 37:20–28
Vicente R, Noel D, Pers YM, Apparailly F, Jorgensen C (2016) Deregulation and therapeutic potential of microRNAs in arthritic diseases. Nat Rev Rheumatol 12:211–220
Vigorito E, Kohlhaas S, Lu D, Leyland R (2013) miR-155: an ancient regulator of the immune system. Immunol Rev 253:146–157
Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z et al (2007) microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847–859
Wang H, Moyano AL, Ma Z, Deng Y, Lin Y, et al. (2017) miR-219 cooperates with miR-338 in myelination and promotes myelin repair in the CNS. Dev cell 40: 566-582 e565
Wang J, Wu M, Wen J, Yang K, Li M et al (2014) MicroRNA-155 induction by Mycobacterium Bovis BCG enhances ROS production through targeting SHIP1. Mol Immunol 62:29–36
Waschbisch A, Atiya M, Linker RA, Potapov S, Schwab S et al (2011) Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS One 6:e24604
Wen Y, Zhang X, Dong L, Zhao J, Zhang C et al (2015) Acetylbritannilactone modulates MicroRNA-155-mediated inflammatory response in ischemic cerebral tissues. Mol Med 21:197–209
Wilms H, Sievers J, Rickert U, Rostami-Yazdi M, Mrowietz U et al (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
Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234
Woodbury ME, Freilich RW, Cheng CJ, Asai H, Ikezu S et al (2015) miR-155 is essential for inflammation-induced hippocampal neurogenic dysfunction. J Neurosci 35:9764–9781
Wu Q, Wang Q, Mao G, Dowling CA, Lundy SK et al (2017) Dimethyl fumarate selectively reduces memory T cells and shifts the balance between Th1/Th17 and Th2 in multiple sclerosis patients. J Immunol 198:3069–3080
Wu XY, Fan WD, Fang R, Wu GF (2014) Regulation of microRNA-155 in endothelial inflammation by targeting nuclear factor (NF)-kappaB P65. J Cell Biochem 115:1928–1936
Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM et al (2014) Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211:1533–1549
Yang Y, Ye Y, Su X, He J, Bai W et al (2017) MSCs-derived exosomes and Neuroinflammation, neurogenesis and therapy of traumatic brain injury. Front Cell Neurosci 11:55
Yin Q, McBride J, Fewell C, Lacey M, Wang X et al (2008) MicroRNA-155 is an Epstein-Barr virus-induced gene that modulates Epstein-Barr virus-regulated gene expression pathways. J Virol 82:5295–5306
Yin Q, Wang X, Roberts C, Flemington EK, Lasky JA (2016) Methylation status and AP1 elements are involved in EBV-mediated miR-155 expression in EBV positive lymphoma cells. Virology 494:158–167
Zhang J, Cheng Y, Cui W, Li M, Li B et al (2014) MicroRNA-155 modulates Th1 and Th17 cell differentiation and is associated with multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol 266:56–63
Zhang J, Vandevenne P, Hamdi H, Van Puyvelde M, Zucchi A et al (2015) Micro-RNA-155-mediated control of heme oxygenase 1 (HO-1) is required for restoring adaptively tolerant CD4+ T-cell function in rodents. Eur J Immunol 45:829–842
Zhang J, Zhang ZG, Lu M, Wang X, Shang X et al (2017) MiR-146a promotes remyelination in a cuprizone model of demyelinating injury. Neuroscience 348:252–263
Zheng B, Yin WN, Suzuki T, Zhang XH, Zhang Y et al (2017) Exosome-mediated miR-155 transfer from smooth muscle cells to endothelial cells induces endothelial injury and promotes atherosclerosis. Mol Ther 25:1279–1294
Zhou H, Huang X, Cui H, Luo X, Tang Y et al (2010) miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. Blood 116:5885–5894
Zhu N, Zhang D, Chen S, Liu X, Lin L et al (2011) Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration. Atherosclerosis 215:286–293
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McCoy, C.E. (2017). miR-155 Dysregulation and Therapeutic Intervention in Multiple Sclerosis. In: Xu, D. (eds) Regulation of Inflammatory Signaling in Health and Disease. Advances in Experimental Medicine and Biology, vol 1024. Springer, Singapore. https://doi.org/10.1007/978-981-10-5987-2_5
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