A Critical Role for Mucosal-Associated Invariant T Cells as Regulators and Therapeutic Targets in Systemic Lupus Erythematosus.

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like lymphocytes that are restricted by major histocompatibility complex-related molecule 1 (MR1). In this study, we investigated the role of MAIT cells in the pathogenesis of lupus in Fc?RIIb-/- Yaa mice, a spontaneous animal model of lupus. Using two approaches of MAIT cell deficiency, MR1 knockout animals and a newly synthesized inhibitory MR1 ligand, we demonstrate that MAIT cells augment the disease course of lupus by enhancing autoantibody production and tissue inflammation. MR1 deficiency reduced germinal center responses and T cell responses in these mice. Suppression of MAIT cell activation by the inhibitory MR1 ligand reduced autoantibody production and lupus nephritis in Fc?RIIb-/- Yaa mice. MAIT cells directly enhanced autoantibody production by B cells in vitro. Our results indicate the contribution of MAIT cells to lupus pathology and the potential of these cells as novel therapeutic targets for autoimmune diseases such as lupus.

SUBMITTER: Murayama G 

PROVIDER: S-EPMC6895065 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature