Sex hormones and gender influence the expression of Foxp3 and regulatory T cells in SLE patients (115.18)

Abstract

Abstract Regulatory T cells have been implicated in the maintenance of immune tolerance. Whether sex hormones and gender influence the expression of FoxP3 and regulatory T cells remain obscure. We provide the first evidence in this study that numbers and percent expression of regulatory T cells are significantly reduced in healthy females compared to healthy males. We found that both CD4+CD25+hi and CD8+CD25hi+ subsets of healthy males had 3-4-fold higher Foxp3 mRNA compared to healthy females. Estrogen increases proinflammatory cytokines and plasma estradiol positively correlated with IL-21 in SLE pts. Levels of estradiol positively correlated with SLEDAI score. Testosterone level was decreased in SLE women compared to healthy women. Furthermore, testosterone significantly increased FoxP3 expression in CD4+CD25hi cells from women with SLE. Plasma concentrations of testosterone positively correlated with the expression of FoxP3 in Treg. These data demonstrate that women may be more susceptible than men to SLE and other autoimmune diseases in part because many healthy women have fewer regulatory T cells and less FoxP3 expression. In addition, women with SLE, compared to healthy women, seem to have less ability to generate CD4+ Treg in response to physiologic concentrations of 17b-estradiol, whereas testosterone metabolite increases the generation of Tregs. These data suggest that gender and sex hormones influence susceptibility to SLE via their effects on Treg and Foxp3 expression.