Impact Factor 4.716 | CiteScore 4.71
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02681

A critical role for mucosal-associated invariant T cells as regulators and therapeutic targets in systemic lupus erythematosus.

  • 1Department of Immunology, Juntendo University School of Medicine, Japan
  • 2Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Japan
  • 3Department of Nephrology, Juntendo University Faculty of Medicine, Japan
  • 4Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University School of Medicine, Japan
  • 5Toin Human Science and Technology Center, Department of Biomedical Engineering, Toin University of Yokohama, Japan

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 FcγRIIb-/-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 FcγRIIb-/-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.

Keywords: MAIT cell, innate lymphocyte, MR1 ligand, lupus, T-B interaction

Received: 13 Sep 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Murayama, Chiba, Suzuki, Nomura, Mizuno, Kuga, Nakamura, Amano, Hirose, Yamaji, Suzuki, Tamura and Miyake. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
MD, PhD. Asako Chiba, Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan,
Prof. Saschiko Miyake, Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan,