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

Research Project

Project/Area Number 26461473
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionJuntendo 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
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (20 results)

All 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 5 results) Book (2 results)

  • [Journal Article] Activation status of mucosal-associated invariant T cells reflects disease activity and pathology of systemic lupus erythematosus2016

    • Author(s)
      Asako Chiba, Naoto Tamura, Kazunori Yoshikiyo, Goh Murayama, Mie Kitagaichi, Ken Yamaji, Yoshinari Takasaki, Sachiko Miyake
    • Journal Title

      Arthritis Research & Therapy

      Volume: 19(1) Issue: 1 Pages: 58-58

    • DOI

      10.1186/s13075-017-1257-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of Mucosal-associated Invariant T cells in Ankylosing Spondylitis2016

    • Author(s)
      Hayashi E, Chiba A, Tada k, Haga K, Kitagaichi M, Nakajima S, Kusaoi M, Sekiya F, Ogasawara M, Yamaji K, Tamura N, Takasaki Y, Miyake S
    • Journal Title

      Journal of Rheumatology

      Volume: 43(9) Issue: 9 Pages: 1695-1703

    • DOI

      10.3899/jrheum.151133

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Role of mucosal-associated invariant T (MAIT) cells in a murine model of lupus.2016

    • Author(s)
      G Murayama A Chiba K Yamaji N Tamura Y Takasaki S Miyake
    • Organizer
      The 45th Annual Meeting of the Japanese Society for Immunology.
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Activation Status of Mucosal-associated Invariant T cells Sensitively Reflects Disease Activity of Systemic Lupus Erythematosus.2016

    • Author(s)
      A Chiba, G Murayama, N Tamura, K Yamaji, Y Takasaki, S Miyake
    • Organizer
      ACR/ARHP Annual Meeting 2016
    • Place of Presentation
      Walter E.Washington Convention Center(米国、ワシントンDC)
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of mucosal-associated invariant T (MAIT) cells in a murine model of lupus.2016

    • Author(s)
      G Murayama, A Chiba, K Yamaji, N Tamura, Y Takasaki, S Miyake
    • Organizer
      ACR/ARHP Annual Meeting 2016
    • Place of Presentation
      Walter E.Washington Convention Center(米国、ワシントンDC)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ループスモデルにおけるMAIT細胞に関する解析2016

    • Author(s)
      村山 豪、千葉麻子、山路健、田村直人、三宅幸子
    • Organizer
      第44回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of mucosal-associated invariant T (MAIT) cells in a murine model of lupus.2016

    • Author(s)
      G Murayama A Chiba K Yamaji N Tamura Y Takasaki S Miyake
    • Organizer
      The 13th International Workshop on Autoantibodies and Autoimmunity
    • Place of Presentation
      The Westin Miyako Kyoto (京都府東山区)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ループスモデルにおけるMAIT細胞の解析2016

    • Author(s)
      村山豪 、千葉麻子、天野浩文、山路健、田村直人、髙崎芳成、三宅幸子
    • Organizer
      第31回自己免疫研究会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-07-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Activation status of mucosal-associated invariant T cells reflects disease activity of systemic lupus erythematosus.2016

    • Author(s)
      A Chiba, N Tamura, K Yoshikiyo, G Murayama, M Kitagaichi, K Yamaji, Y Takasaki, S Miyake
    • Organizer
      FOCiS 2016
    • Place of Presentation
      Seaport World Trade Center(米国、ボストン)
    • Year and Date
      2016-06-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MAIT細胞の 活性化状態は全身性エリテマトーデスの疾患活動性と病態を反映してい2016

    • Author(s)
      千葉麻子、田村直人、村山豪、北垣内みえ、山路健、髙崎芳成、三宅幸子
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 強直性脊椎炎に おけるMAIT細胞の解2016

    • Author(s)
      林絵利、千葉麻子、多田久里守、山路健、田村直人、高崎芳成、三宅幸子
    • Organizer
      第113回日本内科学会総会・講演会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hyperactivation of MAIT cells due to activation potency of lupus monocytes.2015

    • Author(s)
      Asako Chiba, Go Murayma, Naoto Tamura, Yoshinari Takasaki, Sachiko Miyake
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Hyperactivated state of mucosal-associated invariant T cells due to activation potency of monocytes in systemic lupus erythematous.2015

    • Author(s)
      G Murayama, A Chiba, N Tamura, K Yamaji, Y Takasaki, and S Miyake
    • Organizer
      ACR/ARHP Annual Meeting 2015
    • Place of Presentation
      Moscone Center (San Francisco)
    • Year and Date
      2015-11-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hyperactivation of MAIT cells due to activation potency of lupus monocytes. 2015

    • Author(s)
      Asako Chiba, Ken Yamaji, Naoto Tamura, Yoshinari Takasaki,Sachiko Miyake
    • Organizer
      第2回JCRベーシックリサーチカンファレンス
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Involvement of MAIT cells in human autoimmune diseases.2014

    • Author(s)
      Asako Chiba,Naoto Tamura,Yoshinari Takasaki,Sachiko Miyake
    • Organizer
      The 43rd Annual Meeting of The Japanese Society of Immunology
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Reduction of MAIT Cell Frequency Associated with Enhanced Cell Death in Systemic Lupus Erythematosus2014

    • Author(s)
      Asako Chiba,Naoto Tamura,Eri Hayashi,Yoshinari Takasaki,Sachiko Miyake
    • Organizer
      2014 ACR/ARHP Annual Meeting
    • Place of Presentation
      Boston Convention and Exhibition Center, USA
    • Year and Date
      2014-11-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Involvement of IL-17-producing MAIT cells in the pathogenesis of rheumatoid arthritis.2014

    • Author(s)
      Eri Hayashi, Asako Chiba, Mie Kitagaichi, Ken Yamaji, Naoto Tamura,Yoshinari Takasaki, Sachiko Miyake
    • Organizer
      2014 ACR/ARHP Annual Meeting
    • Place of Presentation
      Boston Convention and Exhibition Center, USA
    • Year and Date
      2014-11-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Decreased MAIT cell frequency associated with reduced cell proliferation and enhanced cell death in systemic lupus erythematosus.2014

    • Author(s)
      Asako Chiba,Naoto Tamura,Eri Hayashi, Ran Matsudaira,Yoshinari Takasaki,Sachiko Miyake
    • Organizer
      第58回日本リウマチ学会総会・学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪
    • Year and Date
      2014-04-26
    • Related Report
      2014 Research-status Report
  • [Book] NKT細胞による自己免疫疾患の制御2014

    • Author(s)
      千葉麻子
    • Total Pages
      454
    • Publisher
      科学評論社
    • Related Report
      2014 Research-status Report
  • [Book] 自己免疫におけるMAIT細胞の役割2014

    • Author(s)
      千葉麻子
    • Total Pages
      532
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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