Females are more susceptible than males to most autoimmune diseases. MS is no exception to this as there are sex-biased differences in the incidence, age of onset, and clinical course of MS. Not only are women nearly three times more likely than men to develop MS, they are also more likely to present at a younger age and exhibit a RR-MS course. In contrast, men are diagnosed later and more frequently exhibit a PP-MS course. The SJL mouse model of EAE recapitulates this sex dimorphism: SJL female mice exhibit a higher incidence, more severe disease, and a more consistent relapsing pattern than their male counterparts. We are studying the male- and female-specific differences in the activities of several immune cells, including mast cells and innate lymphoid cells, to understand how they contribute to distinct disease susceptibility.