Retinoic Acid Receptor-Related Receptor Alpha Ameliorates Autoimmune Arthritis via Inhibiting of Th17 Cells and Osteoclastogenesis

• Published in: Frontiers in immunology 2019-10, Vol.10, p.2270-2270
• Main 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
• Format: Article
• Language: English
• Subjects: IL-17-producing T cells; Immunology; osteoclastogenesis; regulatory T cells; rheumatoid arthritis; RORα
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02270

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 (RORα) is a negative regulator of inflammatory responses, whereas RORγt, another member of the ROR family, is a Th17 lineage-specific transcription factor. Here, we investigated the immunoregulatory potential of RORα in collagen-induced arthritis (CIA) mice, an experimental model of RA. Cholesterol sulfate (CS) or SR1078, a ligand of RORα, inhibited RORγt expression and Th17 differentiation . In addition, fortification of RORα in T cells inhibited the expression levels of glycolysis-associated genes. We found that RORα overexpression in CIA mice attenuated the clinical and histological severities of inflammatory arthritis. The anti-arthritic effect of RORα was associated with suppressed Th17 differentiation and attenuated mTOR-STAT3 signaling in T cells. Furthermore, altered RORα activity could directly affect osteoclastogenesis implicated in progressive bone destruction in human RA. Our findings defined a critical role of RORα in the pathogenesis of RA. These data suggest that RORα may have novel therapeutic uses in the treatment of RA.