Oestrogen modulates experimental autoimmune encephalomyelitis and interleukin-17 production via programmed death 1

The mechanism by which oestrogens suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is only partially understood. We here demonstrate that treatment with 17 beta-oestradiol (E-2) in C57BL/6 mice boosted the expression of programmed death 1 (PD-1), a negative regulator of immune responses, in the CD4(+) FoxP3(+) regulatory T (Treg) cell compartment in a dose-dependent manner that correlated with the efficiency of EAE protection. Administration of E-2 at pregnancy levels but not lower concentrations also enhanced the frequency of Treg cells. Additionally, E-2 treatment drastically reduced the production of interleukin-17 (IL-17) in the periphery of immunized mice. However, E-2 treatment did not protect against EAE or suppress IL-17 production in PD-1 gene-deficient mice. Finally, E-2 failed to prevent Treg-deficient mice from developing spontaneous EAE. Taken together, our results suggest that E-2-induced protection against EAE is mediated by upregulation of PD-1 expression within the Treg-cell compartment.