Roles of innate immune cells in opportunistic infections

• Project/Area Number: 26430084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Hokkaido University
• Principal Investigator: Sugimoto Chie 北海道大学, 医学研究科, 助教 (60469955)
• Co-Investigator(Kenkyū-buntansha): 若尾 宏 獨協医科大学, 医学部, 特任教授 (10280950) ; 藤田 博美 獨協医科大学, 医学部, 特任教授 (60142931)
• Research Collaborator: KURODA Marcelo J. Tulane University, Professor
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: MAIT細胞 / 自然免疫型T細胞 / 動物モデル / 自然免疫系T細胞 / アカゲザル

Outline of Final Research Achievements

MAIT cells are a novel subset of innate like T cells which could be associated with susceptibility to opportunistic infections in immune compromised patients. Although MAIT cells are very abundant in humans, there is no suitable animal model for studying MAIT cells due to a very low frequency in laboratory mice. The aim of this study was to establish MAIT animal models. (1) Rhesus monkey model for AIDS-related opportunistic infections: We have detected MAIT cells in peripheral blood from healthy rhesus monkeys by using anti-human antibodies. That frequency was similar to humans. (2) Novel MAIT mouse model: We have established iPS cells derived from MAIT cells in C57BL/6 mice and observed that the iPS cells re-differenciated into MAIT cells using the OP9 feeder cell system. The mouse MAIT-iPS cells will be applied to construct novel mouse MAIT models for future studies.

Research Products

• [Journal Article] Epigenetic silencing of V(D)J recombination is a major determinant for selective differentiation of mucosal-associated invariant t cells from induced pluripotent stem cells. (2017)
  • Author(s): Yutaka Saito, Chie Sugimoto, Toutai Mituyama and Hiroshi Wakao
  • Journal Title: PLoS One Volume: 12 Issue: 3 Pages: e0174699-e0174699
  • DOI: 10.1371/journal.pone.0174699
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The dynamics of mucosal-associated invariant T cells in multiple sclerosis (2016)
  • Author(s): Chie Sugimoto, Makoto Hirotan, Kazunori Yoshikiyo, Uichi Koshimizu, Rika Wakao, Takahiro Horinouchi, Yuichi Mazaki, Tsunehiko Higashi, Toshiyuki Fukazawa, Hiroyoshi Fujita, Hidenao Sasaki and Hiroshi Wakao
  • Journal Title: SpringerPlus Volume: 5 Issue: 1 Pages: 1259-1259
  • DOI: 10.1186/s40064-016-2923-9
  • NAID: 120005906931
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differentiation Kinetics of Blood Monocytes and Dendritic Cells in Macaques: Insights to Understanding Human Myeloid Cell Development. (2015)
  • Author(s): Chie Sugimoto, Atsuhiko Hasegawa, Yohei Saito, Yayoi Fukuyo, Kevin B Chiu, Yanhui Cai, Matthew W Breed, Kazuyasu Mori, Chad J Roy, Andrew A Lackner, Woong-Ki Kim, Elizabeth S Didier and Marcelo J Kuroda
  • Journal Title: Journal of Immunology Volume: 195 Issue: 4 Pages: 1774-1781
  • DOI: 10.4049/jimmunol.1500522
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Preferential Destruction of Interstitial Macrophages over Alveolar Macrophages as a Cause of Pulmonary Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques. (2015)
  • Author(s): Yanhui Cai, Chie Sugimoto, Mariluz Arainga, Cecily C Midkiff, David Xianhong Liu, Xavier Alvarez, Andrew A Lackner, Woong-Ki Kim, Elizabeth S Didier and Marcelo J Kuroda
  • Journal Title: Journal of Immunology Volume: 195 Issue: 10 Pages: 4884-4891
  • DOI: 10.4049/jimmunol.1501194
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Increased monocyte turnover is associated with interstitial macrophage accumulation and pulmonary tissue damage in SIV-infected rhesus macaques. (2015)
  • Author(s): Yanhui Cai, Chie Sugimoto, David Xianhong Liu, Cecily C Midkiff, Xavier Alvarez, Andrew A Lackner, Woong-Ki Kim, Elizabeth S Didier and Marcelo J Kuroda
  • Journal Title: Journal of Leukocyte Biology Volume: 97 Issue: 6 Pages: 1147-1153
  • DOI: 10.1189/jlb.4a0914-441r
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis. (2015)
  • Author(s): Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H
  • Journal Title: PLOS ONE Volume: 10
  • NAID: 120005611266
  • Peer Reviewed / Open Access
• [Presentation] 加齢による粘膜関連インバリアントT細胞の表現系の変化 (2017)
  • Author(s): 杉本智恵、佐々木秀直、若尾宏
  • Organizer: 第87回日本衛生学会
  • Place of Presentation: フェニックスシーガイアリゾート（宮崎県・宮崎市）
  • Year and Date: 2017-03-26
• [Presentation] iPS細胞からの自然免疫型T細胞分化誘導の分子機序の統合的解析 (2016)
  • Author(s): 若尾宏、杉本智恵、満山統泰、斎藤裕
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-11-30
• [Presentation] iPS細胞からのヒト自然免疫型T細胞大量産生系の確立 (2015)
  • Author(s): 杉本智恵、若尾宏
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県、神戸市）
  • Year and Date: 2015-12-01
• [Presentation] HIV感染者での日和見感染症発症における自然免疫系細胞の重要性 (2014)
  • Author(s): 杉本智恵、若尾宏、藤田博美
  • Organizer: 日本生化学会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2014-10-18
• [Presentation] エイズ患者での日和見感染発症における自然免疫系細胞の重要性と新規バイオマーカーの検索 (2014)
  • Author(s): 杉本智恵、若尾宏、藤田博美
  • Organizer: 日本衛生学会
  • Place of Presentation: 岡山コンベンションセンター（岡山県・岡山市）
  • Year and Date: 2014-05-27