Dimethyl fumarate promotes B cell-mediated anti-inflammatory cytokine profile in B and T cells, and inhibits immune cell migration in patients with MS.

Abstract Dimethyl Fumarate (DMF), known for its mechanism of action targeting Nrf2 and related redox homeostasis, is an approved immunotherapy for patients with Multiple Sclerosis (PwMS) in the relapsing form. We assessed how DMF modulates immune cell functions, namely the cytokine profile of co-cultured B and T cells, and the chemokine-mediated migration of immune cells. Following DMF therapy, LTα+, TNFα+ and IFNγ+ B cells were reduced while TGFβ and IL10 expression elevated. B cells from DMF-treated patients increased TGFβ and LTα expression on T cells, while DMF directly reduced TNFα+ and IFNγ+ T cells. CXCL12/CXCL13-mediated migration of B cells, Monocytes, CD4 and CD8 T cells was reduced, with altered CXCR5 and CXCR4 expression. Induction of regulatory B and T cells and reduced migration of immune cells may be part of the beneficial mechanism of DMF in PwMS.