Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis

MS is an autoimmune disease of the CNS that afflicts over 2.5 million people worldwide. There are striking sex differences in the susceptibility to and progression of this disease in humans. Females are twice as likely to develop MS than males, whereas disease progression and disability is more rapid in males compared with females; however, the latter is still controversial. There is growing evidence, mainly from animal models, that innate and adaptive immune responses are different in males and females, and that this can influence the outcome of a range of diseases including infection, cancer, and autoimmunity. Since MS is an immune-mediated disease, sex differences in pathogenic immune responses may account for some of the differences in susceptibility to and progression seen in men versus women. Indeed, data from the mouse model of MS, EAE, have already provided some evidence that female mice have earlier disease onset associated with stronger Th17 responses. This review will discuss the possible immunological basis of sex differences in susceptibility and disease outcome in EAE and MS and how a better understanding of sex differences in the responses to disease-modifying therapies may lead to improved patient treatment.