Development of novel approaches for suppressing atherosclerosis by MAIT cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kitasato University
• Principal Investigator: IWABUCHI KAZUYA 北里大学, 医学部, 教授 (20184898)
• Co-Investigator(Kenkyū-buntansha): SATOH Masashi 北里大学, 医学部, 助教 (40611843)
• Co-Investigator(Renkei-kenkyūsha): ISHIMORI Naoki 北海道大学, 病院, 准教授 (70399848)
• Research Collaborator: FUJII Satoshi 旭川医科大学, 医学部, 教授 (90291228) ; SHIMANO Kentaro ; FUJITA Koki ; OHISHI Yuhta ; HOSHINO Miyuki ; Gilfillan Susan Washington Univ ; Luc Van Kaer Vanderbilt Univ
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: MAIT細胞 / 動脈硬化症 / NKT細胞 / 動物モデル / 自然T細胞 / アポリポタンパクEノックアウトマウス / 炎症制御 / 生活習慣病

Outline of Final Research Achievements

Development of atherosclerosis was ameliorated in NKT cell-deficient mice and aggravated in MAIT cell-deficient apoE knockout (KO) mice. We assumed that a reciprocal regulatory circuit controls the disease process since NKT cells appeared to be activated in MR1-deficient apoE KO mice where the MAIT cells were absent. Although a reciprocal activation of MAIT cells in CD1d-deficient apoE KO mice was not confirmed, we established MR1/CD1d/apoE triple knockout (TKO) mice where both MAIT and NKT cells were dificeint in apoE KO background to test whether the atherosclerotic lesion size either decreased or were similar to the lesion size of MR1-deficient apoE KO mice. In TKO, however, the lseion size was increased compared to the one of MR1/apoE double KO (DKO) mice with the presence of increased NK1.1+ Vβ5+ T cells , suggesting that a minimal regulatory circuit consisted of iNKT and MAIT cells is not sufficient to explain a rather complex process of the development of atherosclerosis.

Free Research Field

Immunology