B Cell Maturation Antigen Inhibits an Inflammatory Role of Testosterone in Experimental Autoimmune Encephalomyelitis in C57BL/6 mice.

Abstract

Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Sex influences both the incidence and prognosis of MS, with the disease more prevalent in women than men. Yet, men experience a more severe disease compared to women. The interplay of immune cells, hormones, and genetics may contribute to these phenomena. In experimental autoimmune encephalomyelitis (EAE) model of MS, there are no discernible effects of sex hormones in C57BL/6 mice. However, we now report an unexpected role of BCMA in controlling an inflammatory function of testosterone in C57BL/6 mice during EAE. BCMA, a cytokine receptor with established effects on B cells, was previously shown to attenuate EAE. We now show sex differences in EAE in BCMA-deficient C57BL/6 mice. Like other reports, we show no differences in the severity of EAE in male and female BCMA+/+ mice. However, the BCMA-/- males had significantly increased paralysis and CNS inflammation compared to BCMA-/- females. Remarkably, castration of BCMA-/- males significantly reduced EAE compared to sham controls, which was not observed in the BCMA+/+ males. In addition, we found that administration of testosterone pellets elevated EAE in male and female BCMA-/- mice. Previous EAE studies have shown a protective effect of testosterone in mice with genetic backgrounds other than C57BL/6. We now show a novel function for BCMA, where it inhibits a paradoxical inflammatory role for testosterone during EAE in C57BL/6 mice.