Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice

Abstract

Immoderate immunoreaction of antigen-specific Th17 and Treg cell dysfunction play critical roles in the pathogenesis of multiple sclerosis. We examined Th17/Treg immune responses and the underlying mechanisms in response to metformin in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Metformin reduced Th17 and increased Treg cell percentages along with the levels of associated cytokines. Molecules involved in cellular metabolism were altered in mice with EAE. Suppressed activation of mTOR and its downstream target, HIF-1α, likely mediated the protective effects of metformin. Our findings demonstrate that regulation of T cell metabolism represents a new therapeutic target for CNS autoimmune disorders.

Keywords: AMPK/mTOR; Experimental autoimmune encephalomyelitis; Metformin; Multiple sclerosis; Th17 cells; Treg cells.