title: Deficiency of β-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell differentiation.
abstract: Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (T(H)17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator β-arrestin1 was significantly up-regulated in peripheral and synovial CD4(+) T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of β-arrestin1 ameliorated disease with decreased T(H)17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that β-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for T(H)17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for β-arrestin1 in the pathogenesis of collagen-induced arthritis and T(H)17 cell differentiation and suggest β-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.forename: Ao
authors.initials: A
authors.lastname: Guo
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Shichao
authors.initials: S
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Chunde
authors.initials: C
authors.lastname: Bao
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology*; D015854:Up-Regulation; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D020381:Interleukin-17; D050796:STAT3 Transcription Factor; D000071557:beta-Arrestins; D053613:Janus Kinase 1