title: MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination.
abstract: MicroRNAs (miRNAs) are an emerging group of short, noncoding RNAs that play an important role in regulating expression of classical genes. Thus far little is known about their role in autoimmune demyelination. In this study, we analyzed changes in the miRNA profile in CD4(+) T cells that occurred during the recognition of the myelin autoantigen, MOG(35-55). We found that, both in vivo and in vitro, myelin antigen stimulation resulted in significant up-regulation of miR-301a, miR-21, and miR-155. Furthermore, these three miRNAs were overexpressed in T cells infiltrating the CNS in animals with experimental autoimmune encephalomyelitis. Use of specific miRNA antagonists, antagomirs, revealed that miR-301a contributed to the development of the T-helper type 17 subset via targeting the IL-6/23-STAT3 pathway. This contribution appeared to be mediated by the miR-301a effect on the expression of the PIAS3, a potent inhibitor of the STAT3 pathway. Manipulation of miR-301a levels or PIAS3 expression in myelin-specific CD4(+) T cells led to significant changes in the severity of experimental autoimmune encephalomyelitis. Thus, we have identified a role of miR-301a in regulating the function of myelin-reactive T-helper type 17 cells, supporting a role for miR-301a and PIAS3 as candidates for therapeutic targets for controlling of autoimmune demyelination.
authors.affiliation: Laboratory of Neuroimmunology, Department of Neurology,  Medical University of Lodz, 90-153, Lodz,  Poland.
authors.forename: Marcin P
authors.initials: MP
authors.lastname: Mycko
authors.forename: Maria
authors.initials: M
authors.lastname: Cichalewska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Machlanska
authors.forename: Hanna
authors.initials: H
authors.lastname: Cwiklinska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mariasiewicz
authors.forename: Krzysztof W
authors.initials: KW
authors.lastname: Selmaj
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D008156:Luciferases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D018709:Statistics, Nonparametric; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C573832:MIRN301 microRNA, mouse; D035683:MicroRNAs; D050828:Protein Inhibitors of Activated STAT; C499308:Rag2 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D008156:Luciferases