Analysis of autophagy deficiency-related disease by mouse model

• Project/Area Number: 21700448
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: Osaka University
• Principal Investigator: SAITOH Tatsuya Osaka University, 微生物病研究所, 助教 (60456936)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: オートファジー / 自然免疫 / 感染症 / 炎症 / メンブレントラフィック / Antophagy / Innate imunnitv / Interferon / Membrane traffic / Lipid droplets / Autophagy / Innate imunnity

Research Abstract

We have examined a role of autophagy in the regulation of innate immune response using mutant mice deficient in autophagy-related protein. We generated Atg9a-deficient mice and found that Atg9a controls dsDNA-induced innate immune response in embryonic fibroblasts. Because aberrant activation of innate immune response by dsDNA often results in the development of massive inflammation, a regulation of Atg9a function might be useful for the therapy of inflammatory disease induced by dsDNA.

Research Products

• [Journal Article] Crohn disease : A current perspective on genetics, autophagy and immunity. (2011)
  • Author(s): Stappenbeck TS, Rioux JD, Mizoguchi A, Saitoh T, Huett A, Darfeuille-Michaud A, Wileman T, Mizushima N, Carding S, Akira S, Parkes M, Xavier RJ (All authors equally contributed to this work)
  • Journal Title: Autophagy. 7(4) Pages: 355-374
  • Peer Reviewed
• [Journal Article] Antiviral Protein Viperin Promotes Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Type I Interferon Production in Plasmacytoid Dendritic Cells. (2011)
  • Author(s): Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S.
  • Journal Title: Immunity 34(3) Pages: 352-63
  • Peer Reviewed
• [Journal Article] Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells (2011)
  • Author(s): Saitoh T, et al.
  • Journal Title: Immunity Volume: (印刷中 In press)
  • Peer Reviewed
• [Journal Article] Crohn disease : A current perspective on genetics, autophagy and immunity (2011)
  • Author(s): Stappenbeck TS, et al.(All authors are equally contributed)
  • Journal Title: Autophagy Volume: (印刷中 In press)
• [Journal Article] The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA. (2010)
  • Author(s): Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, Kawai T, Akira S.
  • Journal Title: Immunity. 33(5) Pages: 765-776
  • Peer Reviewed
• [Journal Article] The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. (2010)
  • Author(s): Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S.
  • Journal Title: Nat Immunol. 11(10) Pages: 936-944
  • Peer Reviewed
• [Journal Article] Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. (2010)
  • Author(s): Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, Izumi T, Noda T, Yoshimori T.
  • Journal Title: J Cell Biol. 190(4) Pages: 511-521
  • Peer Reviewed
• [Journal Article] Regulation of innate immune responses by autophagy-related proteins. (2010)
  • Author(s): Saitoh T, Akira S.
  • Journal Title: J Cell Biol.Review. 189(6) Pages: 925-935
  • Peer Reviewed
• [Journal Article] Regulation of dsDNA-induced innate immune responses by membrane trafficking. (2010)
  • Author(s): Saitoh T, Fujita N, Yoshimori T, Akira S.
  • Journal Title: Autophagy. Review. 6(3) Pages: 430-432
• [Journal Article] Regulation of innate immune responses by autophagy-related proteins (2010)
  • Author(s): Saitoh T, Akira S.
  • Journal Title: J Cell Biol. Volume: 189 Pages: 925-935
  • Peer Reviewed
• [Journal Article] インフラマソームを介した炎症性サイトカインIL-1βの産生 (2010)
  • Author(s): 齊藤達哉、審良静男
  • Journal Title: 医学のあゆみ Volume: 234 Pages: 379-385
• [Journal Article] インフラマソームによる炎症性サイトカインIL-1βの産生制御 (2010)
  • Author(s): 齊藤達哉、審良静男
  • Journal Title: 実験医学 Volume: 28 Pages: 1869-1873
• [Journal Article] Involvement of the NLRP3 Inflammasome in Innate and Humoral Adaptive Immune Responses to Fungal-Glucan. (2009)
  • Author(s): Kumar H, Kumagai Y, Tsuchida T, Koenig PA, Satoh T, Guo Z, Jang MH, Saitoh T, Akira S, Kawai T.
  • Journal Title: J Immunol. 183(12) Pages: 8061-8067
  • Peer Reviewed
• [Journal Article] Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. (2009)
  • Author(s): Saitoh T*, Fujita N*, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T, Yamamoto N, Kawai T, Ishii K, Takeuchi O, Yoshimori T, Akira S
  • Journal Title: (*Equally contributed) Proc Natl Acad Sci U S A. 106(49) Pages: 20842-20846
  • Peer Reviewed
• [Journal Article] Differencial involvement of ATG16L1 in Crohn's disease and canonical autophagy: analysis of the organization of the ATG16L1 complex in fibroblasts. (2009)
  • Author(s): Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T.
  • Journal Title: J Biol Chem. 284(47) Pages: 32602-32609
  • Peer Reviewed
• [Journal Article] Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. (2009)
  • Author(s): Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T.
  • Journal Title: Nat Cell Biol. 11(4) Pages: 385-396
  • Peer Reviewed
• [Journal Article] Atg9a controls dsDNA-driven dynamic translocation of STNG and the innate immune response. (2009)
  • Author(s): Saitoh T, et al.
  • Journal Title: Proc Natl Acad Sci USA. 106 Pages: 20842-20846
  • Peer Reviewed
• [Journal Article] オートファジーと自然免疫 (2009)
  • Author(s): 齊藤逹哉、審良静男
  • Journal Title: 臨床検査 53 Pages: 1562-1568
• [Journal Article] オートファジーと免疫 (2009)
  • Author(s): 齊藤逹哉、審良静男
  • Journal Title: 実験医学 27 Pages: 2969-2974
• [Presentation] 形質細胞様樹状細胞によるTLR7/9を介したI型Interferonの産生においてユビキチンとオートファジー関連因子が果たす役割 (2010)
  • Author(s): 齊藤達哉、審良静男
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)、ポスター発表
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 形質細胞様樹状細胞によるTLR7/9を介したI型Interferonの産生においてユビキチンとオートファジー関連因子が果たす役割 (2010)
  • Author(s): 齊藤達哉、審良静男
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸、日本
  • Year and Date: 2010-12-08
• [Presentation] Regulation of nucleic acid-induced innate immune responses by membrane trafficking (2010)
  • Author(s): Saitoh T, Fujita N, Yoshimori T, Akira S.
  • Organizer: The 14th International Congress of Immunology, Oral presentation, Kobe
  • Place of Presentation: Japan
  • Year and Date: 2010-08-27
• [Presentation] Regulation of nucleic acid-induced innate immune responses by membrane trafficking (2010)
  • Author(s): Saitoh T, Fujita N, Yoshimori T, Akira S
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-27
• [Presentation] オートファジー関連因子Atg9aの欠失は二重鎖DNA刺激による膜蛋白質STINGの移行を介した自然免疫応答を促進する (2010)
  • Author(s): 齊藤達哉、藤田尚信、吉森保、審良静男
  • Organizer: 第62回日本細胞生物学会年会、ポスター発表
  • Place of Presentation: 大阪
• [Presentation] オートファジー関連因子Atg9aの欠失は二重鎖DNA刺激による膜蛋白質STINGの移行を介した自然免疫応答を促進する (2010)
  • Author(s): 齊藤達哉、藤田尚信、吉森保、審良静男
  • Organizer: 第62回日本細胞生物学会年会
  • Place of Presentation: 大阪、日本
• [Presentation] オートファジー関連因子による自然免疫応答の制御 (2009)
  • Author(s): 齊藤達哉、藤田尚信、吉森保、審良静男
  • Organizer: 第32回日本分子生物学会年会、ワークショップ口頭発表
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Regulation of innate immune response by autophagy-related protein. (2009)
  • Author(s): Saitoh T, Fujita N, Yoshimori T, Akira S.
  • Organizer: The 5th International Symposium on Autophagy, Oral presentation, Otsu
  • Place of Presentation: Japan
  • Year and Date: 2009-09-27
• [Presentation] Regulation of innate immune response (2009)
  • Author(s): Saitoh T, Fujita N, Yoshimori T, Akira S
  • Organizer: The 5th International Symposium on Autophagy
  • Place of Presentation: Otsu, Japan
  • Year and Date: 2009-09-27
• [Remarks] ホームページ等
  • URL: http://hostdefense.ifrec.osaka-u.ac.jp/ja/index.html
• [Remarks]
  • URL: http://hostdefense.ifrec.osaka-u.ac.jp/ja/index.html