Decreased Gaq expression in T cells correlates with enhanced cytokine production and disease activity in systemic lupus erythematosus

Abstract

Aberrant T cell immune responses appear central to the development of systemic lupus erythematosus (SLE). We previously reported that Gaq, the alpha subunit of Gq, regulates T and B cell immune responses, promoting autoimmunity. To address whether Gaq contributes to the pathogenesis of SLE, Gaq mRNA expression was studied using real time-PCR in PBMCs and T cells from SLE patients as well as age- and sex-matched healthy controls. Our results showed that Gaq mRNA expression was decreased in PBMCs and T cells from SLE patients compared to healthy individuals. Correlation analyses showed that Gaq expression in T cells from SLE patients was associated with disease severity (as per SLE Disease Activity Index), the presence of lupus nephritis, and expression of Th1, Th2 and Th17 cytokines. In keeping with clinical results, T-helper cell subsets (Th1, Th2 and Th17) were over-represented in Gaq knockout mice. In addition, Gaq expression in SLE T cells was negatively correlated with the expression of Bcl-2, an anti-apoptotic gene, and positively correlated with the expression of Bax, a pro-apoptotic gene. These data suggest that reduced Gaq levels in T cells may promote enhanced and prolonged T cell activation, contributing to the clinical manifestations of SLE.