title: microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis.
abstract: microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17-92 expression resulted in exacerbated experimental autoimmune encephalitis and failure to establish clinical remission. Using peptide-MHC tetramers, we demonstrate that the miR-17-92 cluster was specifically required for the accumulation of activated Ag-specific Treg and for differentiation into IL-10-producing effector Treg.
authors.affiliation: Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Dimitri
authors.initials: D
authors.lastname: de Kouchkovsky
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Esensten
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Rosenthal
authors.forename: Malika M
authors.initials: MM
authors.lastname: Morar
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Lukas T
authors.initials: LT
authors.lastname: Jeker
mesh_terms: D000328:Adult; D000818:Animals; D017951:Antigen Presentation; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D018106:CD28 Antigens / Q000276:immunology; D002478:Cells, Cultured; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D017353:Gene Deletion; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D051059:PTEN Phosphohydrolase / Q000172:deficiency; D010446:Peptide Fragments / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D018106:CD28 Antigens; D061025:Costimulatory and Inhibitory T-Cell Receptors; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; C556062:IL10 protein, mouse; C568997:MIR17HG, human; C575895:MIRN17-92 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse