Progesterone suppresses Th17 cell responses, and enhances the development of regulatory T cells, through thymic stromal lymphopoietin-dependent mechanisms in experimental gonococcal genital tract infection

Abstract

In most female patients, the symptoms of genital infection due to Neisseria gonorrhoeae tend to be slight or even absent. Our previous studies suggested that progesterone might play a role in female asymptomatic gonococcal infection. In this study, we demonstrated that progesterone induced the expression of thymic stromal lymphopoietin (TSLP) and regulatory T cells (Treg)-related transcription factor Foxp3, and inhibited the expression of Th17 related transcription factor RORγt, and reduced the influx of neutrophils in murine vaginal gonococcal infection. Blockade of TSLP with antibody partially reversed the effects of progesterone on the murine model of gonococcal vaginal infection. In in vitro experiments, progesterone induced a rapid up-regulation of TSLP in vaginal epithelial cells stimulated with N. gonorrhoeae. Blocking thymic stromal lymphopoietin receptor (TSLPR) with a TSLPR monoclonal antibody partially prevented progesterone suppression of IL-17-producing T cells differentiation, and progesterone promotion of CD4+CD25+Foxp3+ regulatory T cells differentiation. Altogether, our results indicate that the progesterone suppresses Th17 cell responses, and enhances the development of Treg cells, through TSLP-dependent mechanisms, and play a role in female asymptomatic gonococcal infections.