[25]. Our results indicated that dysregulation of IL-10 and its

receptor in CD4+ and CD8+ T cells may play an important role Selleckchem BAY 57-1293 in the pathogenesis and development of LN, a particular subtype of SLE, but not in all SLE patients. T cells are thought to play a central role in the regulation of the immune system. They activate B cell functions, including the production of autoantibodies, and initiate renal disease by increasing intrarenal nephritogenic cytokines [26–28]. Simultaneous blockading of the B7/CD28 and CD40/gp39 co-stimulation pathways could produce beneficial effects in murine lupus [29]. With regard to the effects of IL-10 on T cells, studies have proved that IL-10 administration results in the direct and indirect inhibition of T cell functions [30–33]. IL-10 administration was also reported to convert responder T cells into IL-10 producers, acting to suppress inflammatory responses [34]. In addition, some studies have demonstrated that IL-10R1 expression plays a critical role in determining whether cells respond to IL-10 [35–37]. Pictilisib Because we found that IL-10R1 expression levels on CD4+ T cells and CD8+ T cells were correlated negatively with SLE disease activity, and the STAT-3 phosphorylation of PBMCs upon IL-10 stimulation were delayed and down-regulated

in LN and active patients, we hypothesized that IL-10R expression and signalling down-regulation may lead to a poorer response of effector T cells to the inhibitory signals of IL-10. These effects could result

in T cell activation, followed by initiation or enhancement of autoimmune pathogenesis in LN patients. However, the mechanisms Non-specific serine/threonine protein kinase of IL-10R1 expression and signalling down-regulation in CD4+ and CD8+ cells are not yet clear. In this study, we found a negative correlation between plasma IL-10 and IL-10R1 levels on CD4+ and CD8+ T cells. A previous study has shown that the expression of IL-10R1 mRNA was down-regulated after activation in some human T cell clones [38]. These results indicated that circulatory IL-10 and its receptor on T cells may have some regulatory effect on each other. In Caucasian populations, IL-10R1 sense polymorphisms S138G and G330R were proved to be loss-of-function alleles, which could influence IL-10-induced STAT-1 and STAT-3 activation, and G330R may possibly contribute to RA or SLE disease susceptibility [39,40]. However, in the Han populations of China, we have detected IL-10R1 sense polymorphism within exon, but found no contribution to SLE susceptibility (data not shown). Therefore, further research is required to elucidate the mechanism of IL-10R1 expression and signalling down-regulation in CD4+ and CD8+ T cells in LN patients, and to elucidate whether the down-regulation of IL-10R1 expression is a pathogenic factor or a result of an abnormal phenotype.