Activation mechanisms of lupus MAIT cells and their roles in lupus pathology.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: CHIBA Asako 順天堂大学, 医学部, 准教授 (40532726)
• Research Collaborator: MURAYAMA Goh 順天堂大学, 大学院・医学研究科, 大学院生 ; KITAGAICHI Mie 順天堂大学, 大学院・医学研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 全身性エリテマトーデス / 自然リンパ球 / MAIT細胞 / ループスマウスモデル

Outline of Final Research Achievements

Previously we found that the frequency of Mucosal-associated invariant T (MAIT) cells is reduced patially due to activation-induced cell death in patients with systemic lupus erythematosus (SLE) . In this study, we elucidated two possible mechanisms of MAIT cell activation in SLE. We revealed that monocytes from lupus patients exhibited an increased ability to induce MAIT cell activation. We also found MAIT cells were activated by cytokines including IL-18 and IFNalpha, important key players in lupus pathology. Next, we investigated the role of MAIT cells in FcγRIIb-/- Yaa lupus model mice. The lack of MR1 improved survival rate and reduced serum levels of anti-dsDNA antibody. There was a trend of reduced glomerulonephritis and glomerular IgG deposits in MR1-/- FcγRIIb-/- Yaa mice. On the contrary, MR1-/- FcγRIIb-/- Yaa mice developed exacerbated dermatitis. Further studies are required to reveal mechanisms by which MAIT cells are involved in lupus pathology.

Free Research Field

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