Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis

摘要

Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate. We also show that the M-SOB effect on EAE susceptibility is associated with differential production of multiple cytokines/chemokines by neuroantigen-specific T cells that are known to play a role in EAE pathogenesis. Taken together, these results support the existence of an M-SOB effect that may reflect seasonally dependent developmental differences in adaptive immune responses to self-antigens independent of external stimuli, including exposure to sunlight and vitamin D. Moreover, our documentation of an M-SOB effect on EAE susceptibility in mice allows for modeling and detailed analysis of mechanisms that underlie the M-SOB effect in not only MS but in numerous other diseases in which M-SOB impacts susceptibility.—Reynolds, J. D., Case, L. K., Krementsov, D. N., Raza, A., Bartiss, R., Teuscher, C. Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.