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CR6‐interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells
Author(s) -
Park JinSil,
Choi SiYoung,
Hwang SunHee,
Kim SungMin,
Choi JeongWon,
Jung KyungAh,
Kwon Ji Ye,
Kong YoungYun,
Cho MiLa,
Park SungHwan
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13042
Subject(s) - arthritis , biology , immunology , stat protein , microbiology and biotechnology , autoimmune disease , transcription factor , cancer research , signal transduction , antibody , stat3 , gene , biochemistry
Summary CR 6‐interacting factor 1 ( CRIF 1) is a nuclear protein that interacts with other nuclear factors and androgen receptors, and is implicated in the regulation of cell cycle progression and cell growth. In this study, we examined whether CRIF1 exerts an immunoregulatory effect by modulating the differentiation and function of pathogenic T cells. To this end, the role of CRIF 1 in rheumatoid arthritis, a systemic autoimmune disease characterized by hyperplasia of synovial tissue and progressive destruction of articular cartilage structure by pathogenic immune cells [such as T helper type 17 (Th17) cells], was investigated. p3 XFLAG ‐ CMV ‐10‐ CRIF 1 was administered to mice with collagen‐induced arthritis 8 days after collagen type II immunization and the disease severity and histologic evaluation, and osteoclastogenesis were assessed. CRIF 1 over‐expression in mice with collagen‐induced arthritis attenuated the clinical and histological signs of inflammatory arthritis. Furthermore, over‐expression of CRIF 1 in mice with arthritis significantly reduced the number of signal transducer and activator of transcription 3‐mediated Th17 cells in the spleen as well as osteoclast differentiation from bone marrow cells. To investigate the impact of loss of CRIF 1 in T cells, we generated a conditional CRIF 1 gene ablation model using CD 4‐cre transgenic mice and examined the frequency of Th17 cells and regulatory T cells. Deficiency of CRIF1 in CD 4 + cells promoted the production of interleukin‐17 and reduced the frequency of regulatory T cells. These results suggest a role for CRIF1 in modulating the activities of Th17 cells and osteoclasts in rheumatoid arthritis.