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

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...

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Detalles Bibliográficos
Autores principales: Murayama, Goh, Chiba, Asako, Suzuki, Hitoshi, Nomura, Atsushi, Mizuno, Tomohiro, Kuga, Taiga, Nakamura, Shinji, Amano, Hirofumi, Hirose, Sachiko, Yamaji, Ken, Suzuki, Yusuke, Tamura, Naoto, Miyake, Sachiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895065/
https://www.ncbi.nlm.nih.gov/pubmed/31849932
http://dx.doi.org/10.3389/fimmu.2019.02681
Descripción
Sumario: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.