Molecular basis of gamma delta T cell exhaustion during malaria

• Project/Area Number: 18K07094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Nagasaki University
• Principal Investigator: INOUE Shin-Ichi 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (20466030)
• Co-Investigator(Kenkyū-buntansha): 小林 富美恵 麻布大学, 生命・環境科学部, 客員教授 (20118889) ; 新倉 保 杏林大学, 医学部, 講師 (30407019)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: γδT細胞 / マラリア / T細胞疲弊 / γδ T細胞 / γδ T cell / malaria / T cell exhaustion

Outline of Final Research Achievements

Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. Recently it has been reported that repeated infection of Plasmodium falciparum associated with loss and dysfunction of Vδ2+γδ T cells. Here we investigate the molecular mechanism of γδT cell exhaustion by microarray analysis using mouse malaria model. We found candidates of the γδT cell exhaustion-associated molecules.

Academic Significance and Societal Importance of the Research Achievements

γδ T細胞は様々な病原体に対する免疫応答のみならず、自己免疫疾患やガン免疫においても重要な役割を担うことが知られている。しかし、“γδ T細胞疲弊”に関する報告はほとんど無い。生体内でγδ T細胞疲弊が起こっていることが発見されたのがつい最近であるために、非常に新規性の高い研究対象である。本研究では、γδ T細胞疲弊が起こる分子機序の手がかりとなる分子群を明らかにすることができた。そして、本研究が推進されることで得られる知見は、マラリア免疫のみならず、γδ T細胞が関与する種々の感染免疫や自己免疫疾患やガン免疫などの様々な研究に波及効果をもたらすと期待できる。

Research Products

• [Int'l Joint Research] PGIMER(インド)
• [Int'l Joint Research] PGIMER(インド)
• [Int'l Joint Research] PGIMER(インド)
• [Journal Article] Host-pathogen interaction in the tissue environment during Plasmodium blood-stage infection (2021)
  • Author(s): K. Yui, S. Inoue
  • Journal Title: Parasite Immunol Volume: 43 Issue: 2
  • DOI: 10.1111/pim.12763
  • Peer Reviewed
• [Journal Article] G-strand Binding Protein 2 is Involved in Asexual and Sexual Development of Plasmodium berghei (2020)
  • Author(s): Niikura M, Fukutomi T, Fukui K, Inoue SI, Asahi H, Kobayashi F
  • Journal Title: Parasitology International Volume: － Pages: 102059-102059
  • DOI: 10.1016/j.parint.2020.102059
  • Peer Reviewed
• [Journal Article] Activation and IL-10 production of specific CD4+ T cells are regulated by IL-27 during chronic infection with Plasmodium chabaudi. (2020)
  • Author(s): Sukhbaatar O, Kimura D, Miyakoda M, Nakamae S, Kimura K, Hara H, Yoshida H, Inoue SI, Yui K.
  • Journal Title: Parasitol Int. Volume: 74 Pages: 101994-101994
  • DOI: 10.1016/j.parint.2019.101994
  • NAID: 120006988377
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of IL-10 in inhibiting protective immune responses against infection with heterologous Plasmodium parasites (2019)
  • Author(s): Nakamae Sayuri、Kimura Daisuke、Miyakoda Mana、Sukhbaatar Odsuren、Inoue Shin-Ichi、Yui Katsuyuki
  • Journal Title: Parasitology International Volume: 70 Pages: 5-15
  • DOI: 10.1016/j.parint.2019.01.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マラリアに対する防御免疫においてγδT細胞が果たす役割 (2019)
  • Author(s): 井上信一、小林富美惠、由井克之
  • Journal Title: 臨床免疫・アレルギー科 Volume: 71 Pages: 252-257
• [Journal Article] γδ T cells modulate humoral immunity against Plasmodium berghei infection (2018)
  • Author(s): Inoue Shin-Ichi、Niikura Mamoru、Asahi Hiroko、Kawakami Yasushi、Kobayashi Fumie
  • Journal Title: Immunology Volume: 155 Issue: 4 Pages: 519-532
  • DOI: 10.1111/imm.12997
  • Peer Reviewed
• [Journal Article] Comparative genomics and proteomic analyses between lethal and nonlethal strains of Plasmodium berghei. (2018)
  • Author(s): Mamoru Niikura, Shin-Ichi Inoue, Toshiyuki Fukutomi, Junya Yamagishi, Hiroko Asahi, Fumie Kobayashi
  • Journal Title: Experimental Parasitology Volume: 185 Pages: 1-9
  • DOI: 10.1016/j.exppara.2018.01.001
  • Peer Reviewed
• [Presentation] マラリア原虫感染応答での原虫特異的CD4+T細胞の分化決定におけるγδ T細胞の役割 (2021)
  • Author(s): 井上信一,Bayarsaikhan Ganchimeg,Jian Jiun-Yu,Odsuren Sukhbaatar,Ntita Mbaya,Tsogtsaikhan Sanjaadorj,Malou Maccalinao,木村一美,Daniel Fernandez-Ruiz, William Heath, 由井克之
  • Organizer: 第90回 日本寄生虫学会大会
• [Presentation] マラリアによるγδ T細胞疲弊の分子基盤解明に向けた研究 (2020)
  • Author(s): 井上信一,Bayarsaikhan Ganchimeg,Jian Jiun-Yu,Odsuren Sukhbaatar,Ntita Mbaya,Tsogtsaikhan Sanjaadorj,Malou Maccalinao,木村一美,朝日博子,新倉保,小林富美惠,由井克之
  • Organizer: 第89回 日本寄生虫学会大会
• [Presentation] γδ T cell-exhaustion during Plasmodium infection (2020)
  • Author(s): Shin-Ichi Inoue、Bayarsaikhan Ganchimeg、Jian Jiun-Yu、Odsuren Sukhbaatar、Ntita Mbaya、Tsogtsaikhan Sanjaadorj、Malou Maccalinao、Kazumi Kimura、Hiroko Asahi、Mamoru Niikura、Fumie Kobayashi、Katsuyuki Yui
  • Organizer: 第13回寄生虫感染免疫研究会
• [Presentation] γδ T cells regulate humoral immunity against Plasmodium berghei infection (2019)
  • Author(s): 井上信一、Bayarsaikhan Ganchimeg、 Jian Jiun-Yu、 Odsuren Sukhbaatar、Ntita Mbaya、Tsogtsaikhan Sanjaadorj、木村一美、新倉保、小林富美惠、由井克之
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Roles of γδ T cells in protective immunity to malaria (2019)
  • Author(s): Shin-Ichi Inoue
  • Organizer: 2nd Medical Sciences Cluster Infectious Disease Symposium & 14th NUS-Nagasaki Joint Symposium
  • Int'l Joint Research
• [Presentation] マラリアによるγδT細胞疲弊の誘導 (2019)
  • Author(s): 井上信一, Bayarsaikhan Ganchimega, Jian Jiun-Yua, Odsuren Sukhbaatara, Ntita Mbayaa, Tsogtsaikhan, Sanjaadorja, 木村一美, 新倉保, 小林富美惠, 由井克之
  • Organizer: 2019年度日本寄生虫学会南日本支部大会
• [Presentation] γδ T cells play a crucial role for protective immunity to Plasmodium infection (2019)
  • Author(s): Shin-Ichi Inoue, Bayarsaikhan Ganchimeg, Jian Jiun-Yu, Odsuren Sukhbaatar, Ntita Mbaya, Tsogtsaikhan Sanjaadorj, Kazumi Kimura, Mamoru Niikura Fumie Kobayashi, Katsuyuki Yui
  • Organizer: ID-RiPS
• [Presentation] γδ T cells modulate humoral immunity against Plasmodium berghei infection (2019)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi, Katsuyuki Yui
  • Organizer: 第88回 日本寄生虫学会大会
• [Presentation] γδ T cells modulate humoral immunity against Plasmodium berghei infection (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi, Katsuyuki Yui
  • Organizer: 第71回 日本寄生虫学会 南日本支部大会
• [Presentation] Preferential response of Vγ1+ γδ T cells during Plasmodium berghei infection (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Fumie Kobayashi
  • Organizer: 第47回 日本免疫学会学術集会
• [Presentation] γδ T cell-related protective immunity against Plasmodium berghei (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi
  • Organizer: ICOPA2018
  • Int'l Joint Research / Invited
• [Presentation] Role of γδ T cells in protective immunity against malaria (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi
  • Organizer: Scientific Symposium of Japan-India Research Exchange Projects within “Strategic International Research Cooperative Program (SICP)”
  • Int'l Joint Research / Invited
• [Presentation] γδT cells are crucial for protective immunity against malaria． (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi
  • Organizer: The 19th Forum Cheju
• [Presentation] Vγ1＋γδT細胞によるマラリア原虫感染防御機構の解明． (2018)
  • Author(s): Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Fumie Kobayashi
  • Organizer: 第87回 日本寄生虫学会大会
• [Presentation] Immunological memory to malaria is impaired by Salmonella infection (2018)
  • Author(s): Inoue SI，Niikura M，Asahi H，Kurata S，Osaki K，Kamiya S，Kobayashi F
  • Organizer: 第11回寄生虫感染免疫研究会
• [Remarks] 研究室ホームページ
  • URL: https://www.med.nagasaki-u.ac.jp/mmi/im/introduction/index.html
• [Remarks] 研究室ホームページ
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/im/introduction/index.html