The role of PI3K-Akt-mTORC1 signaling pathway on Th17 differentiation

• Project/Area Number: 24790479
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University (2013); Keio University (2012)
• Principal Investigator: NAGAI Shigenori 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (50348801)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Th17 / PI3K / mTORC1 / mTORC / p70S6K / Th17分化 / Akt

Research Abstract

Th17 cell is a kind of helper T (Th) cells which causes autoimmune diseases such as rheumatoid arthritis or inflammatory bowel disease. Therefore, to clarify the molecular mechanisms of Th17 differentiation is thought to lead the effective prevention or the development of the effective therapy. In this research, we demonstrated that phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 signaling pathway positively regulates Th17 differentiation.

Research Products

• [Journal Article] TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads to reduced antigen presentation and increased immune tolerance. (2013)
  • Author(s): Baghdadi M, Yoneda A, Yamashina T, Nagao H, Komohara Y, Nagai S, Akiba H, Foretz M, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Takeya M, Viollet B, Yagita H, Jinushi M
  • Journal Title: Immunity Volume: 39 Issue: 6 Pages: 1070-1081
  • DOI: 10.1016/j.immuni.2013.09.014
  • Peer Reviewed
• [Journal Article] A unique dermal dendritic cell subset that skews the immune response toward Th2. (2013)
  • Author(s): 2.Murakami R, Denda-Nagai K, Hashimoto S, Nagai S, Hattori M, Irimura T.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e73270-e73270
  • DOI: 10.1371/journal.pone.0073270
  • Peer Reviewed / Open Access
• [Journal Article] CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice. (2013)
  • Author(s): Yoshida H, Kotani H, Kondo T, Tani I, Wei X, Tsuruta S, Kimura A, Asakawa M, Ito M, Nagai S, Yoshimura A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 435 Issue: 3 Pages: 378-384
  • DOI: 10.1016/j.bbrc.2013.04.096
  • Peer Reviewed
• [Journal Article] Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation (2013)
  • Author(s): Nagai S, Kurebayashi Y, Koyasu S
  • Journal Title: Ann N Y Acad Sci Volume: 1280 Issue: 1 Pages: 30-4
  • DOI: 10.1111/nyas.12059
  • Peer Reviewed
• [Journal Article] Recent advances in understanding the molecular mechanisms of the development and function of Th17 cells. (2013)
  • Author(s): Kurebayashi Y, Nagai S, Ikejiri A, Koyasu S.
  • Journal Title: Genes to Cells Volume: 18 Issue: 4 Pages: 247-265
  • DOI: 10.1111/gtc.12039
  • Peer Reviewed
• [Journal Article] Local effects of regulatory T cells in MUC1 transgenic mice potentiate growth of MUC1 expressing tumor cells in vivo (2012)
  • Author(s): Sugiura D, Denda-Nagai K, Takashima M,他全7名
  • Journal Title: PLos One Volume: 7 (9) Issue: 9 Pages: e44770-e44770
  • DOI: 10.1371/journal.pone.0044770
  • Peer Reviewed
• [Journal Article] PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi-1 expression and nuclear translocation of RORγ (2012)
  • Author(s): Kurebayashi Y. Nagai S. Ikejiri A. Ohtani M. Ichiyama K. Baba Y. Yamada T. Egami S. Hoshii T. Hirao A. Matsuda S. Koyasu S.
  • Journal Title: Cell Reports Volume: 1 Issue: 4 Pages: 360-373
  • DOI: 10.1016/j.celrep.2012.02.007
  • Peer Reviewed
• [Journal Article] Autoimmunity against M(2) muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype (2012)
  • Author(s): Yoshizawa, A.
  • Journal Title: Eur J Immunol Volume: 42 Issue: 5 Pages: 1152-1163
  • DOI: 10.1002/eji.201142104
  • Peer Reviewed
• [Presentation] 超音波照射はインプラント表面のバイオフィルムを除去しインプラント関連感染症(IAI)の発症を予防する (2013)
  • Author(s): 吉岡研之、石井賢、永井重徳、柿沼祐亮、佐々木文、相澤守、岡田保典、小安重夫、戸山芳昭、松本守雄
  • Organizer: 第25回整形外科超音波学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-07-06
• [Presentation] Development of a novel antimicrobial - coated biomedical polymer (2013)
  • Author(s): Ishihama H, Ishii K, Nagai S, Kakinuma H, Sasaki A, Yoshioka K, Kuramoto T, Shiono Y, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS)
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] A comparison of biofilm formation in various metal materials (2013)
  • Author(s): Yosihoka K, Ishii K, Nagai S, Kakinuma H, Kuramoto T, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS) 2013
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] Propionibacterium acnes causes delayed surgical site infection only in the presence of implant (2013)
  • Author(s): Shiono Y, Ishii K, Nagai S, Kuramoto T, Yoshioka K, Ishihama H, Funao H, Kakinuma H, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS) 2013
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] Cellular response of immunocyte to boron - containing apatite ceramics (2013)
  • Author(s): Nakamura M, Zhuang Z, Umeda R, Nagai S, Aizawa M
  • Organizer: The 2nd International Symposium on Inorganic and Environmental Materials (ISIEM) 2013
  • Place of Presentation: Rennes, France
• [Presentation] The pathogenesis of pulmonary alveolar proteinosis in PI3K deficient mice (2013)
  • Author(s): Shigenori Nagai, Akihiro Yoshizawa, Yukiko Baba, Taketo Yamada, Tomoyasu Nishimura, Shigeo Koyasu
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張
• [Presentation] Resident memory T cells in epidermis require hair follicle - derived cytokines for survival (2013)
  • Author(s): Takeya Adachi, Kazuyo Moro, Shigenori Nagai, Masayuki Amagai, Keisuke Nagao
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張
• [Presentation] Development of pulmonary alveolar proteinosis in PI3K deficient mice (2013)
  • Author(s): Akihiro Yoshizawa, Shigenori Nagai, Yukiko Baba, Tomoyasu Nishimura, Taketo Yamada, Shigeo Koyasu
  • Organizer: The Joint International Meeting of The 78^<th> Meeting of the Japanese Society of Interferon and Cytokine Research and The 21^<st> International Symposium on Molecular Cell Biology of Macrophages 2013
  • Place of Presentation: Tokyo
• [Presentation] Development of a novel antimicrobial-coated biomedical polymer. (2013)
  • Author(s): Ishihama H, Ishii K, Nagai S, Kakinuma H, Sasaki A, Yoshioka K, Kuramoto T, Shiono Y, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M.
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS) 2013.
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] A comparison of biofilm formation in various metal materials. (2013)
  • Author(s): Yosihoka K, Ishii K, Nagai S, Kakinuma H, Kuramoto T, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M.
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS) 2013.
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] Propionibacterium acnes causes delayed surgical site infection only in the presence of implant. (2013)
  • Author(s): Shiono Y, Ishii K, Nagai S, Kuramoto T, Yoshioka K, Ishihama H, Funao H, Kakinuma H, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M.
  • Organizer: The International Society for the Study of Lumbar Spine (ISSLS) 2013.
  • Place of Presentation: Scottsdale, Arizona, USA
• [Presentation] Cellular response of immunocyte to boron-containing apatite ceramics. (2013)
  • Author(s): Nakamura M, Zhuang Z, Umeda R, Nagai S, Aizawa M.
  • Organizer: The 2nd International Symposium on Inorganic and Environmental Materials (ISIEM) 2013.
  • Place of Presentation: Rennes, France
• [Presentation] The pathogenesis of pulmonary alveolar proteinosis in PI3K deficient mice. (2013)
  • Author(s): Shigenori Nagai, Akihiro Yoshizawa, Yukiko Baba, Taketo Yamada, Tomoyasu Nishimura, Shigeo Koyasu
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] Resident memory T cells in epidermis require hair follicle-derived cytokines for survival. (2013)
  • Author(s): Takeya Adachi, Kazuyo Moro, Shigenori Nagai, Masayuki Amagai, Keisuke Nagao.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] Development of pulmonary alveolar proteinosis in PI3K deficient mice. (2013)
  • Author(s): Akihiro Yoshizawa, Shigenori Nagai, Yukiko Baba, Tomoyasu Nishimura, Taketo Yamada, Shigeo Koyasu
  • Organizer: The Joint International Meeting of The 78th JSICR and The 21st MMCB
  • Place of Presentation: 都市センターホテル（東京都千代田区）
• [Presentation] 超音波照射はインプラント表面のバイオフィルムを除去しインプラント関連感染症 (IAI) の発症を予防する (2013)
  • Author(s): 吉岡研之、石井賢、永井重徳、柿沼祐亮、佐々木文、相澤守、岡田保典、小安重夫、戸山芳昭、松本守雄
  • Organizer: 第25回整形外科超音波学会学術集会
  • Place of Presentation: ウエスティンナゴヤキャッスル（愛知県名古屋市）
• [Presentation] 獲得免疫系におけるmTORC1シグナルの役割 (2012)
  • Author(s): 松田達志,永井重徳,星居孝之,小安重夫,平尾敦,大谷真志
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] PI3K-Akt-mTORC1-S6K1/2 Axis Controls Th17 Differentiation (2012)
  • Author(s): Shigenori Nagai, Yutaka Kurebayashi, Ai Ikejiri, Masashi Ohtani, Kenji Ichiyama, Yukiko Baba, Taketo Yamada, Shohei Egami, Takayuki Hoshii, Atsushi Hirao, Satoshi Matsuda, Shigeo Koyasu
  • Organizer: Inositol Phospholipid Signaling in Physiology and Disease, New York Academy of Sciences
  • Place of Presentation: NY,USA
• [Presentation] TIM-4 blockade augments therapeutic efficacy of chemotherapy by immune-mediated mechanisms (2012)
  • Author(s): Baghdadi Muhammad, Shigeki Chiba, Hisaya Akiba, Hideo Yagita, Shigenori Nagai, Masahisa Jinushi
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] Recognition of amphiphilic acylglucoside derived from Helicobacter pylori by C-type lectin receptor Mincle (2012)
  • Author(s): Masahiro Nagata, Michio Shimamura, Eri Ishikawa, Shigenori Nagai, Shigeo Koyasu, Sho Yamasaki
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] PI3K-Akt-mTORC1-S6K1/2経路はGfi1の発現およびRORの核移行を調節することによりTh17分化を制御する (2012)
  • Author(s): 永井重徳,紅林泰,大谷真志,松田達志,小安重夫
  • Organizer: 第22回Kyoto T cell Conference
  • Place of Presentation: 京都
• [Presentation] 樹状細胞移入による新規コラーゲン誘導関節炎モデルの確立 (2012)
  • Author(s): 永井重徳,小安重夫
  • Organizer: 第56回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Role of TLRs in the induction of collagen-induced arthritis (2012)
  • Author(s): Midori Iso, Shigenori Nagai, Shigeo Koyasu
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
• [Presentation] PI3K-Akt-mTORC1-S6K経路はTh17分化を制御する (2012)
  • Author(s): 永井重徳,紅林泰,池尻藍,大谷真志,馬場夕紀子,星居孝之,平尾敦,松田達志,小安重夫
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Role of TLRs in the induction of collagen-induced arthritis (2012)
  • Author(s): Midori Iso, Shigenori Nagai, Shigeo Koyasu
  • Organizer: The 12th International Symposium on Dendritic Cells
  • Place of Presentation: Daegu, Korea
• [Presentation] Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling (2012)
  • Author(s): Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Shigeo Koyasu and Keiichi Fukuda
  • Organizer: 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: Tokyo
• [Presentation] 獲得免疫系におけるmTORC1シグナルの役割 (2012)
  • Author(s): 松田達志，永井重徳，星居孝之，小安重夫，平尾敦，大谷真志
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡国際会議場
  • Invited
• [Presentation] PI3K-Akt-mTORC1-S6K1/2 Axis Controls Th17 Differentiation． (2012)
  • Author(s): Shigenori Nagai, Yutaka Kurebayashi, Ai Ikejiri, Masashi Ohtani, Kenji Ichiyama, Yukiko Baba, Taketo Yamada, Shohei Egami, Takayuki Hoshii, Atsushi Hirao, Satoshi Matsuda, Shigeo Koyasu
  • Organizer: Inositol Phospholipid Signaling in Physiology and Disease, New York Academy of Sciences
  • Place of Presentation: World Trade Center Building, New York, USA
  • Invited
• [Presentation] TIM-4 blockade augments therapeutic efficacy of chemotherapy by immune-mediated mechanisms. (2012)
  • Author(s): Baghdadi Muhammad, Shigeki Chiba, Hisaya Akiba, Hideo Yagita, Shigenori Nagai, Masahisa Jinushi
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Recognition of amphiphilic acylglucoside derived from Helicobacter pylori by C-type lectin receptor Mincle. (2012)
  • Author(s): Masahiro Nagata, Michio Shimamura, Eri Ishikawa, Shigenori Nagai, Shigeo Koyasu, Sho Yamasaki
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Role of TLRs in the induction of collagen-induced arthritis. (2012)
  • Author(s): Midori Iso, Shigenori Nagai, Shigeo Koyasu
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] PI3K-Akt-mTORC1-S6K経路はTh17分化を制御する (2012)
  • Author(s): 永井重徳，紅林泰，池尻藍，大谷真志，馬場夕紀子，星居孝之，平尾敦，松田達志，小安重夫
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Role of TLRs in the induction of collagen-induced arthritis. (2012)
  • Author(s): Midori Iso, Shigenori Nagai, Shigeo Koyasu
  • Organizer: The 12th International Symposium on Dendritic Cells
  • Place of Presentation: EXCO, Daegu, Korea
• [Presentation] Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. (2012)
  • Author(s): Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Shigeo Koyasu and Keiichi Fukuda
  • Organizer: 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: 東京大学山上会館
• [Remarks]
  • URL: http://www.tmd.ac.jp/mim/
• [Remarks] JST，慶應義塾大学共同発表：自己免疫疾患の原因となる免疫細胞が増える新たな仕組みを発見
  • URL: http://www.jst.go.jp/pr/announce/20120330/
• [Remarks] 慶應義塾大学医学部 微生物学・免疫学教室 小安研究室 2012年研究業績
  • URL: http://www.koyasu.umin.ne.jp/publications%202012.html