title: MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression.
abstract: Th17 cells are central to the pathogenesis of autoimmune disease, and recently specific noncoding microRNAs have been shown to regulate their development. However, it remains unclear whether microRNAs are also involved in modulating Th17 cell effector functions. Consequently, we examined the role of miR-155 in differentiated Th17 cells during their induction of experimental autoimmune encephalomyelitis. Using adoptive transfer experiments, we found that highly purified, myelin oligodendrocyte glycoprotein Ag-specific Th17 cells lacking miR-155 were defective in their capacity to cause experimental autoimmune encephalomyelitis. Gene expression profiling of purified miR-155(-/-)IL-17F(+) Th17 cells identified a subset of effector genes that are dependent on miR-155 for their proper expression through a mechanism involving repression of the transcription factor Ets1. Among the genes reduced in the absence of miR-155 was IL-23R, resulting in miR-155(-/-) Th17 cells being hyporesponsive to IL-23. Taken together, our study demonstrates a critical role for miR-155 in Th17 cells as they unleash autoimmune inflammation and finds that this occurs through a signaling network involving miR-155, Ets1, and the clinically relevant IL-23-IL-23R pathway.
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Ruozhen
authors.initials: R
authors.lastname: Hu
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Huffaker
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Kagele
authors.forename: Marah C
authors.initials: MC
authors.lastname: Runtsch
authors.forename: Erin
authors.initials: E
authors.lastname: Bake
authors.forename: Aadel A
authors.initials: AA
authors.lastname: Chaudhuri
authors.forename: June L
authors.initials: JL
authors.lastname: Round
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse