CCR5 blockade inhibits menstrual-driven proinflammatory T cell infiltration into the cervicovaginal mucosa of women.

The menstrual cycle influences the development and severity of inflammatory disorders and susceptibility to infections, yet its direct role in shaping mucosal immunity remains poorly defined. Here, we tracked CD4 T cell surveillance in the female reproductive tract (FRT) of cycling women in the presence or absence of the CCR5 antagonist maraviroc. Across the menstrual cycle, we identified dynamic changes consistent with an immune response during the time frame of progesterone withdrawal. Using a murine model of menstruation, we further demonstrate that the endometrial remodeling process drives the recruitment of bystander-activated CD4 T cells into the cervicovaginal tissues in a CCR5-dependent manner. Notably, maraviroc treatment in women led to prolonged receptor antagonism, substantially reducing this immune response. These data demonstrate that menstrual-driven proinflammatory CD4 T cell infiltration into the FRT can be inhibited by CCR5 blockade, which may provide an immunomodulatory approach to treating associated diseases and conditions affecting women.