Development of novel approaches for suppressing atherosclerosis by MAIT cells

• 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
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / 病態モデル / マウス / レパトア解析 / マイクロアレイ / 自然リンパ球 / MR1 / CD1d

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.

Research Products

• [Int'l Joint Research] Vanderbilt University/Washington University(米国)
• [Journal Article] Inhibitory function of NKT cells during early induction phase of nickel allergy. (2016)
  • Author(s): Hironori Okuno, Masashi Satoh, Emiko Takeuchi, Koji Eshima, Masazumi Terashima, Jun Komotori, Sonoko Habu, Hidekazu Tamauchi, Kazuya Iwabuchi.
  • Journal Title: Immunobiology Volume: in press Issue: 7 Pages: 833-838
  • DOI: 10.1016/j.imbio.2016.01.012
  • Peer Reviewed / Open Access
• [Journal Article] Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA. (2016)
  • Author(s): Yamanaka T, Tamauchi H, Suzuki Y, Suzuki H, Horikoshi S, Terashima M, Iwabuchi K, Habu S, Okumura K, Tomino Y.
  • Journal Title: Immunobiol Volume: 221 Issue: 4 Pages: 577-585
  • DOI: 10.1016/j.imbio.2015.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Synovial macrophage-derived IL-1b regulates the calcitonin receptor in osteoarthritic mice. (2016)
  • Author(s): Takano S, Uchida K, Miyagi M, Inoue G, Aikawa J, Fujimaki H, Minatani A, Sato M, Iwabuchi K, Takaso M.
  • Journal Title: Clin Exp Immunol Volume: 183 Issue: 1 Pages: 143-149
  • DOI: 10.1111/cei.12712
  • Peer Reviewed
• [Journal Article] Differential dependence on nuclear factor-κB-inducing kinase among natural killer T-cell subsets in their development. (2015)
  • Author(s): Noma H, Eshima K, Satoh M, Iwabuchi K
  • Journal Title: Immunology Volume: 146 Issue: 1 Pages: 89-99
  • DOI: 10.1111/imm.12484
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CD11c+ macrophages and levels of TNF-α and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidemia. (2015)
  • Author(s): Uchida K, Satoh M, Inoue G, Onuma K, Miyagi M, Iwabuchi K, Takaso M.
  • Journal Title: Exp Clin Immunol Volume: in press Issue: 3 Pages: 551-559
  • DOI: 10.1111/cei.12607
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prostanoid induces premetastatic niche in regional lymph nodes. (2014)
  • Author(s): Ogawa F, Amano H, Eshima Y, Ito Y, Matsui Y, Hosono K, Kitasato H, Iyoda A, Iwabuchi K, Kumagai Y, Satoh Y, Narumiiya S, Majima M.
  • Journal Title: J. Clin. Invest. Volume: 124 Issue: 11 Pages: 4882-4894
  • DOI: 10.1172/jci73530
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phenotypic changes in growth-arrested T cell hybrids: a possible avenue to produce functional T cell hybridoma. (2014)
  • Author(s): Kubota K, Iwabuchi K.
  • Journal Title: Front Immunol Volume: 5
  • DOI: 10.3389/fimmu.2014.00229
  • Peer Reviewed / Open Access
• [Journal Article] Significant Involvement of NF-κB- inducing Kinase in Proper Differentiation ofαβandγδT cells (2014)
  • Author(s): Eshima K
  • Journal Title: Immunology Volume: 41(2) Issue: 2 Pages: 222-32
  • DOI: 10.1111/imm.12186
  • Peer Reviewed / Open Access
• [Journal Article] TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: Ramifications of correlation between plasma S1P levels and metabolic syndrome (2014)
  • Author(s): Shiori Ito
  • Journal Title: Coron. Artery Dis. Volume: 25 Issue: 4 Pages: 311-320
  • DOI: 10.1097/mca.0000000000000082
  • Peer Reviewed
• [Journal Article] Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice (2013)
  • Author(s): Andoh Y, Ogura H, Satoh M, Shimano K, Okuno H, Fujii S, Ishimori N, Eshima K, Tamauchi H, Otani T, Nakai Y, Van Kaer L, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: Immunobiology Volume: 218 Issue: 4 Pages: 561-569
  • DOI: 10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice. (2013)
  • Author(s): Homma T, Kinugawa S, Takahashi M, Sobirin MA, Saito A, Fukushima A, Suga T, Takada S, Kadoguchi T, Masaki Y, Furihata T, Taniguchi M, Nakayama T, Ishimori N, Iwabuchi K, Tsutsui H.
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 62 Pages: 179-188
  • DOI: 10.1016/j.yjmcc.2013.06.004
  • Peer Reviewed
• [Journal Article] Myeloid calcifying cells promote atherosclerotic calcification via paracrine activity and allograft inflammatory factor-1 overexpression. (2013)
  • Author(s): Albiero M, Rattazzi M, Menegazzo L, Boscaro E, Cappellari R, Pagnin E, Bertacco E, Poncina N, Dyar K, Ciciliot S, Iwabuchi K, Millioni R, Arrigoni G, Kraenkel N, Landmesser U, Agostini C, Avogaro A, Fadini GP.
  • Journal Title: Basic Research in Cardiology Volume: 108 Issue: 4 Pages: 368-368
  • DOI: 10.1007/s00395-013-0368-7
  • Peer Reviewed
• [Presentation] Development of Atherosclerotic lesion in mice deficient for both CD1d- and MR1-restricted NKT cells. (2015)
  • Author(s): Fujita K, Satoh M, Hoshino M, Shimano K, Eshima K, Gilfillan S, Miyake S, Van Kaer L, Yamamura T, Iwabuchi K.
  • Organizer: CD1-MR1 2015
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2015-11-15
  • Int'l Joint Research
• [Presentation] NKT cell - adipocyte interaction modulate adipose tissue function. (2015)
  • Author(s): Satoh M, Iwabuchi K.
  • Organizer: CD1-MR1 2015
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2015-11-15
  • Int'l Joint Research
• [Presentation] Atherosclerotic lesion development in CD1d/MR1/apolipoprotein E-deficient mice. (2014)
  • Author(s): Iwabuchi K, Shimano K, Satoh M, Gilfillan S, Miyake S, Van Kaer L, Yamamura T.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto International Conference Center (Kyoto)
  • Year and Date: 2014-12-10
• [Presentation] Adipocytes activate NKT cells via CD1d. (2014)
  • Author(s): Satoh M, Eshima K, Takeuchi ME, Iwabuchi K.
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto International Conference Center (Kyoto)
  • Year and Date: 2014-12-10
• [Presentation] ApoEノックアウトマウスの病巣進展における粘膜関連インバリアントT（MAIT）細胞の役割． (2014)
  • Author(s): 岩渕和也
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島）
  • Year and Date: 2014-04-26
• [Presentation] Development of atherosclerotic lesion is aggravated in MR1-/- mice - an ameliorating role of MR1-restricted NKT cells in atherosclerosis-
  • Author(s): Iwabuchi K, Sato M, Eshima K, Gilfillan S, Miyake S, Yamamura T, Onoe K, Ogura H.
  • Organizer: The 7th International Symposium on CD1 and NKT cells
  • Place of Presentation: Tours, France
• [Presentation] Atherosclerotic lesion development in MR1/apolipoprotein E-deficient mice.
  • Author(s): Shimano K, Sato M, Okuno H, Gilfillan S, Miyake S, Yamamura T, Ogura H, Iwabuchi K.
  • Organizer: The 42nd Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba, Japan
• [Book] 免疫力徹底研究 (2015)
  • Author(s): 岩渕和也
  • Total Pages: 133
  • Publisher: NPO法人 先端医療をささえる会
• [Remarks] 北里大学医学部免疫学・大学院医療系研究科細胞免疫学ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/immunology/
• [Remarks] 北里大学医学部免疫学・大学院医療系研究科細胞免疫学
  • URL: http://www.med.kitasato-u.ac.jp/immunology/
• [Remarks] 北里大学医学部免疫学・大学院医療系研究科細胞免疫学
  • URL: http://www.med.kitasato-u.ac.jp/immunology/