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

The Gαq-containing G protein, an important member of Gq/11 class, is ubiquitously expressed in mammalian cells. Gαq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gαq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gαq controls RA via regulation of Th1 differentiation. We observed that the expression of Gαq was negatively correlated with the expression of signature Th1 cytokine (IFN-γ) in RA patients, which suggests a negative role of Gαq in differentiation of Th1 cells. By using Gαq knockout (Gnaq-/-) mice, we demonstrated that loss of Gαq led to enhanced Th1 cell differentiation. Gαq 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 Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gαq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.

The use of biologic therapies in the treatment of rheumatoid arthritis.

The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past two decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. Biologic agents indeed lead to a better prognosis and clinical remission in patients with RA, especially in patients who are not well-controlled with traditional disease-modifying anti-rheumatic drugs (DMARDs). Currently, five TNF inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol), an IL-6 receptor antagonist (tocilizumab), an IL-1 receptor antagonist (anakinra), a B cell depleting agent (rituximab) and a T cell co-stimulation inhibitor (abatacept) have been approved for the treatment of RA. With the increased understanding of the pathogenic mechanisms of RA and advantages in manufacturing biotechnology of pharmaceutical companies, a series of novel biologic therapeutic approaches are being developed. In the present paper, we will summarize the biologic agents currently available to treat RA, and the prospective biologic therapies that might be used in the management of RA in future.