title: Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice.
abstract: Th17 cells promote a variety of autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TGF-β is required for conversion of naive T cells to Th17 cells, but the mechanisms regulating this process are unknown. Integrin αvβ8 on DCs can activate TGF-β, and this process contributes to the development of induced Tregs. Here, we have now shown that integrin αvβ8 expression on DCs plays a critical role in the differentiation of Th17 cells. Th17 cells were nearly absent in the colons of mice lacking αvβ8 expression on DCs. In addition, these mice and the DCs harvested from them had an impaired ability to convert naive T cells into Th17 cells in vivo and in vitro, respectively. Importantly, mice lacking αvβ8 on DCs showed near-complete protection from experimental autoimmune encephalomyelitis. Our results therefore suggest that the integrin αvβ8 pathway is biologically important and that αvβ8 expression on DCs could be a therapeutic target for the treatment of Th17-driven autoimmune disease.
authors.affiliation: Lung Biology Center, Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Melton
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Bailey-Bucktrout
authors.forename: Mark A
authors.initials: MA
authors.lastname: Travis
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fife
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D066298:In Vitro Techniques; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D017931:DNA Primers; D016023:Integrins; D012333:RNA, Messenger; C403414:integrin alphavbeta8