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

Abstract

MS is an autoimmune disease of the CNS that afflicts over 2.5 million people world-wide. There are striking sex differences in the susceptibility to and progression of thisdisease in humans. Females are twice as likely to develop MS than males, whereas dis-ease 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 thatthis can influence the outcome of a range of diseases including infection, cancer, andautoimmunity. Since MS is an immune-mediated disease, sex differences in pathogenicimmune responses may account for some of the differences in susceptibility to and pro-gression seen in men versus women. Indeed, data from the mouse model of MS, EAE, havealready provided some evidence that female mice have earlier disease onset associatedwith stronger Th17 responses. This review will discuss the possible immunological basisof sex differences in susceptibility and disease outcome in EAE and MS and how a betterunderstanding of sex differences in the responses to disease-modifying therapies maylead to improved patient treatment