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

Goh Murayama; Asako Chiba; Hitoshi Suzuki; Atsushi Nomura; Tomohiro Mizuno; Taiga Kuga; Shinji Nakamura; Hirofumi Amano; Sachiko Hirose; Ken Yamaji; Yusuke Suzuki; Naoto Tamura; Sachiko Miyake

doi:10.3389/fimmu.2019.02681

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

Front Immunol. 2019 Nov 29:10:2681. doi: 10.3389/fimmu.2019.02681. eCollection 2019.

Authors

Goh Murayama^{1

2}, Asako Chiba¹, Hitoshi Suzuki³, Atsushi Nomura¹, Tomohiro Mizuno¹, Taiga Kuga^{1

2}, Shinji Nakamura⁴, Hirofumi Amano², Sachiko Hirose⁵, Ken Yamaji², Yusuke Suzuki³, Naoto Tamura², Sachiko Miyake¹

Affiliations

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

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 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; MR1 ligand; T-B cell interaction; innate lymphocyte; lupus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Lupus Nephritis / immunology*
Lupus Nephritis / pathology*
Mice
Mucosal-Associated Invariant T Cells / immunology*