| First Author | Park JS | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 2270 | PubMed ID | 31636631 |
| Mgi Jnum | J:297959 | Mgi Id | MGI:6479452 |
| Doi | 10.3389/fimmu.2019.02270 | Citation | Park JS, et al. (2019) Retinoic Acid Receptor-Related Receptor Alpha Ameliorates Autoimmune Arthritis via Inhibiting of Th17 Cells and Osteoclastogenesis. Front Immunol 10:2270 |
| abstractText | 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 (RORalpha) is a negative regulator of inflammatory responses, whereas RORgammat, another member of the ROR family, is a Th17 lineage-specific transcription factor. Here, we investigated the immunoregulatory potential of RORalpha in collagen-induced arthritis (CIA) mice, an experimental model of RA. Cholesterol sulfate (CS) or SR1078, a ligand of RORalpha, inhibited RORgammat expression and Th17 differentiation in vitro. In addition, fortification of RORalpha in T cells inhibited the expression levels of glycolysis-associated genes. We found that RORalpha overexpression in CIA mice attenuated the clinical and histological severities of inflammatory arthritis. The anti-arthritic effect of RORalpha was associated with suppressed Th17 differentiation and attenuated mTOR-STAT3 signaling in T cells. Furthermore, altered RORalpha activity could directly affect osteoclastogenesis implicated in progressive bone destruction in human RA. Our findings defined a critical role of RORalpha in the pathogenesis of RA. These data suggest that RORalpha may have novel therapeutic uses in the treatment of RA. |
