Retinoic Acid Receptor-Related Receptor Alpha Ameliorates Autoimmune Arthritis via Inhibiting of Th17 Cells and Osteoclastogenesis
- Authors
- Park, Jin-Sil; Moon, Su-Jin; Lim, Mi-Ae; Byun, Jae-Kyeong; Hwang, Sun-Hee; Yang, SeungCheon; Kim, Eun-Kyung; Lee, Hohyun; Kim, Sung-Min; Lee, Jennifer; Kwok, Seung-Ki; Min, Jun-Ki; Lee, Mi-Ock; Shin, Dong-Yun; Park, Sung-Hwan; Cho, Mi-La
- Issue Date
- 4-Oct-2019
- Publisher
- FRONTIERS MEDIA SA
- Keywords
- rheumatoid arthritis; ROR alpha; IL-17-producing T cells; regulatory T cells; osteoclastogenesis
- Citation
- FRONTIERS IN IMMUNOLOGY, v.10
- Journal Title
- FRONTIERS IN IMMUNOLOGY
- Volume
- 10
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/18056
- DOI
- 10.3389/fimmu.2019.02270
- ISSN
- 1664-3224
- Abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis characterized by progressive joint destruction. IL-17-producing CD4(+) T (Th17) cells play pivotal roles in RA development and progression. Retinoic acid receptor-related orphan receptor alpha (ROR alpha) is a negative regulator of inflammatory responses, whereas ROR gamma t, another member of the ROR family, is a Th17 lineage-specific transcription factor. Here, we investigated the immunoregulatory potential of ROR alpha in collagen-induced arthritis (CIA) mice, an experimental model of RA. Cholesterol sulfate (CS) or SR1078, a ligand of ROR alpha, inhibited ROR gamma t expression and Th17 differentiation in vitro. In addition, fortification of ROR alpha in T cells inhibited the expression levels of glycolysis-associated genes. We found that ROR alpha overexpression in CIA mice attenuated the clinical and histological severities of inflammatory arthritis. The anti-arthritic effect of ROR alpha was associated with suppressed Th17 differentiation and attenuated mTOR-STAT3 signaling in T cells. Furthermore, altered ROR alpha activity could directly affect osteoclastogenesis implicated in progressive bone destruction in human RA. Our findings defined a critical role of ROR alpha in the pathogenesis of RA. These data suggest that ROR alpha may have novel therapeutic uses in the treatment of RA.
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