Gq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation.

The Gq-containing G protein, an important member of class, is ubiquitously expressed in mammalian cells. Gq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gq controls RA via regulation of Th1 differentiation. We observed that the expression of Gq was negatively correlated with the expression of signature Th1 cytokine (IFN-) in RA patients, which suggests a negative role of Gq in differentiation of Th1 cells. By using Gq knockout () mice, we demonstrated that loss of Gq led to enhanced Th1 cell differentiation. Gq negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.