Analysis of the mechanisms of an RNase, Zc3h12a-mediated immune regulation.

• Project/Area Number: 22689016
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyoto University (2012); Osaka University (2010-2011)
• Principal Investigator: TAKEUCHI Osamu 京都大学, ウイルス研究所, 教授 (10379092)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2010: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 炎症 / サイトカイン / mRNA安定性 / 自然免疫 / シグナル伝達 / RNA安定性 / IkBキナーゼ / Zc3h12a / ユビキチン化 / プロテオソーム / Toll-like receptor

Research Abstract

In this study, we examined the role of an RNase Regnase-1 (also known as Zc3h12a) in the prevention of the development of autoimmune diseases, and found that Regnase-1 expressed in T cells as well as macrophages is critical for this task. Furthermore, Regnase-1 protein expression is dramatically regulated in the course of inflammation in these cells.

Research Products

• [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation (2013)
  • Author(s): Uehata T, Iwasaki H, Vandenbon A, Matsushita, K, Hernandez Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O and Akira S
  • Journal Title: Cell Volume: 23;153 Issue: 5 Pages: 1036-49
  • DOI: 10.1016/j.cell.2013.04.034
  • Peer Reviewed
• [Journal Article] Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation (2013)
  • Author(s): Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O
  • Journal Title: J Immunol Volume: 190 Issue: 11 Pages: 5702-11
  • DOI: 10.4049/jimmunol.1203155
  • Peer Reviewed
• [Journal Article] Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages (2013)
  • Author(s): Satoh T, Kidoya H, Naito H, Yamamoto M,Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S
  • Journal Title: Nature Volume: 495 Pages: 524-8
  • Peer Reviewed
• [Journal Article] Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activaion via MAPKs. (2013)
  • Author(s): Ori D
  • Journal Title: J Immunol Volume: 190(8) Issue: 8 Pages: 4037-4045
  • DOI: 10.4049/jimmunol.1300173
  • Peer Reviewed
• [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation (2013)
  • Author(s): Uehata T, Iwasaki H, Vandenbon A, Matsushita K, Hernandez Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O and Akira S
  • Journal Title: Cell Volume: in press
  • Peer Reviewed
• [Journal Article] Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation. (2013)
  • Author(s): Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O.
  • Journal Title: J Immunol. Volume: in press
  • Peer Reviewed
• [Journal Article] Critical role of Trib1 for the differentiation of adipose tissue-resident macrophages maintaining metabolic homeostasis. (2013)
  • Author(s): Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Morii E, Takakura N, Takeuchi O, Akira S
  • Journal Title: Nature Volume: 495(7442) Issue: 7442 Pages: 524-528
  • DOI: 10.1038/nature11930
  • Peer Reviewed
• [Journal Article] The transcription factor Jun dimerization protein 2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation (2012)
  • Author(s): kenta Maruyama, Masahiro Fukasaka, Alexis Vandenbon, Tatsuya Saitoh, Takumi Kawasaki, Takeshi Kondo, Kazunari K. Yokoyama, Hiroyasu Kidoya, Nobuyuki Takakura, Daron Standley, Osamu Takeuchi, and Shizuo Akira
  • Journal Title: Immunity Volume: 37 Issue: 6 Pages: 1024-1036
  • DOI: 10.1016/j.immuni.2012.08.022
  • Peer Reviewed
• [Journal Article] TRAF family member-associated NF-_<K>B activator (TANK) is a negative regulator of osteoclastogenesis and bone formation (2012)
  • Author(s): kenta Maruyama, Tatsukata Kawagoe, Takeshi Kondo, Shizuo Akira, and Osamu Takeuchi.
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 34 Pages: 29114-29124
  • DOI: 10.1074/jbc.m112.347799
  • Peer Reviewed
• [Journal Article] The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice (2012)
  • Author(s): Abe Y, Fujii K, Nagata N, Takeuchi O, Akira S, Oshiumi H, Matsumoto M, Seya T, Koike S
  • Journal Title: J Virol Volume: 86 Pages: 185-194
  • Peer Reviewed
• [Journal Article] The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. (2011)
  • Author(s): Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K, Satoh T, Saitoh T, Matsushita M, Standley DM, Akira S.
  • Journal Title: Nat Immunol. Volume: 12 Issue: 12 Pages: 1167-1175
  • DOI: 10.1038/ni.2137
  • Peer Reviewed
• [Journal Article] The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1 (2011)
  • Author(s): Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K, Satoh T, Saitoh T, Matsushita M, Standley DM, Akira S
  • Journal Title: Nature Immunology Volume: 12 Pages: 1167-1175
  • Peer Reviewed
• [Journal Article] The TRAF-associated protein TANK facilitates cross-talk within the IkappaB kinase family during Toll-like receptor signaling (2011)
  • Author(s): Clark K, Takeuchi O, Akira S, Cohen P
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Pages: 17093-17098
  • Peer Reviewed
• [Journal Article] IκBζ Is Essential for Natural Killer Cell Activation in Response to IL-12 and IL-18 (2010)
  • Author(s): Miyake, T., Satoh, T., Kato, H., Matsushita, K., Kumagai, Y., Vandenbon, A., Tani, T., Muta, T., Akira, S., Takeuchi, O.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Issue: 41 Pages: 17680-17685
  • DOI: 10.1073/pnas.1012977107
  • Peer Reviewed
• [Journal Article] Pattern recognition receptors and inflammation. (2010)
  • Author(s): Takeuchi O, Akira S
  • Journal Title: Cell Volume: 140(6) Issue: 6 Pages: 805-20
  • DOI: 10.1016/j.cell.2010.01.022
• [Journal Article] Pattern recognition receptors and inflammation. (2010)
  • Author(s): Takeuchi, O., Akira, S.
  • Journal Title: Cell Volume: 6 Pages: 805-820
  • Peer Reviewed
• [Journal Article] The Jmjd3-Irf4 axis regulates M2 macropharge polarization and host responses against helminth infection. (2010)
  • Author(s): Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Kumagai, Y., Miyake, T., Matsuyama, T., Yui K., Okazaki, T., Saitoh, T., Honma, K., Nakai, K., Akira, S.
  • Journal Title: Nat Immunol Volume: 11 Pages: 936-944
  • Peer Reviewed
• [Journal Article] I{kappa}B{zeta} is essential for natural killer cell activation in response to IL-12 and IL-18. (2010)
  • Author(s): Miyake, T., Satoh, T., Kato, H., Matsushita, K., Kumagai, Y., Vandenbon, A., Tani, T., Muta, T., Akira, S., Takeuchi, O.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 107 Pages: 17680-17685
  • Peer Reviewed
• [Journal Article] BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. (2010)
  • Author(s): Ren D, Tu HC, Kim H, Wang GX, Bean GR, Takeuchi O, Jeffers JR, Zambetti GP, Hsieh JJ, Cheng EH
  • Journal Title: Science Volume: 330 Pages: 1390-1393
  • Peer Reviewed
• [Journal Article] An Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence. (2010)
  • Author(s): Berger M, Krebs P, Crozat K, Li X, Croker BA, Siggs OM, Popkin D, Du X, Lawson BR, Theofilopoulos AN, Xia Y, Khovananth K, Y Moresco EM, Satoh T, Takeuchi O, Akira S, Beutler B.
  • Journal Title: Nat Immunol Volume: 11 Pages: 335-343
  • Peer Reviewed
• [Journal Article] p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis. (2010)
  • Author(s): Kirsch DG, Santiago PM, di Tomaso E, Sullivan JM, Hou WS, Dayton T, Jeffords LB, Sodha P, Mercer KL, Cohen R, Takeuchi O, Korsmeyer SJ, Bronson RT, Kim CF, Haigis KM, Jain RK, Jacks T.
  • Journal Title: Science Volume: 327 Pages: 593-596
  • Peer Reviewed
• [Presentation] RNA分解酵素Regnase-1による自然免疫制御 (2012)
  • Author(s): 竹内 理
  • Organizer: 日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] Posttranscriptional control of inflammation (2012)
  • Author(s): Takeuchi, O
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Systems Immunology-最近の動向 (2012)
  • Author(s): Takeuchi, O.
  • Organizer: Annual Meeting of Japanese Society for Immunology
  • Place of Presentation: Kobe
• [Presentation] Recognition of viral infection by innate immunity (2012)
  • Author(s): Takeuchi, O
  • Organizer: Single Topic Conference "Hepatitis C: Best Practice Based on Science"
  • Place of Presentation: Tokyo
• [Presentation] Posttranscriptional control of inflammation by an Rnase, Regnase-1 (2012)
  • Author(s): Takeuchi, O
  • Organizer: IEIIS2012
  • Place of Presentation: Tokyo
• [Presentation] Posttranscriptional control of inflammation by an RNase, Regnase-1. (2012)
  • Author(s): Takeuchi, O
  • Organizer: 19th East Asia Joint Symposium on Biomedical Research
  • Place of Presentation: Seoul
• [Presentation] Posttranscriptional control of inflammation. (2012)
  • Author(s): Takeuchi, O.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Review Talk: Systems Immunology―最近の動向. (2012)
  • Author(s): Takeuchi, O.
  • Organizer: Annual Meeting of Japanese Society for Immunology
  • Place of Presentation: Kobe
  • Invited
• [Presentation] Recognition of viral infection by innate immunity. (2012)
  • Author(s): Takeuchi, O.
  • Organizer: Single Topic Conference “Hepatitis C: Best Practice Based on Science”
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] Posttranscriptional control of inflammation by an RNase, Regnase-1. (2012)
  • Author(s): Takeuchi, O
  • Organizer: IEIIS2012
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] Posttranscriptional control of inflammation by an RNase, Regnase-1. (2012)
  • Author(s): Takeuchi, O
  • Organizer: 19th East Asia Joint Symposium on Biomedical Research
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] 自然免疫応答調節メカニズム (2011)
  • Author(s): 竹内理
  • Organizer: 第19回肺リモデリング研究会
  • Place of Presentation: 東京ステーションコンファレンス(東京)(招待講演)
  • Year and Date: 2011-10-15
• [Presentation] RNA分解調節による炎症制御メカニズム (2011)
  • Author(s): 竹内理
  • Organizer: 第75回日本生化学会中部支部例会・シンポジウム
  • Place of Presentation: 静岡県立大学(静岡)(招待講演)
  • Year and Date: 2011-05-28
• [Presentation] Regulation of inflammation by Toll-like receptor-inducible genes (2011)
  • Author(s): Osamu Takeuchi
  • Organizer: International Symposium : Towards comprehensive understanding of Immune Dynamism
  • Place of Presentation: 千里阪急ホテル(大阪)
  • Year and Date: 2011-03-01
• [Presentation] Control of inflammation by Toll-like receptor-inducible genes (2011)
  • Author(s): Osamu Takeuchi
  • Organizer: Avison Biomedical Symposium
  • Place of Presentation: Seoul (Korea)(招待講演)
  • Year and Date: 2011-02-25
• [Presentation] Control of inflammation by Toll-like receptor-inducible genes (2011)
  • Author(s): Osamu Takeuchi
  • Organizer: International Symposium on Cell Dynamics and Bioimaging
  • Place of Presentation: GIST, Gwangju (Korea)(招待講演)
  • Year and Date: 2011-02-23
• [Presentation] Rapid degradation of Zc3h12a to TLR/IL-1R stimulation regulates inflammatory gene expression (2011)
  • Author(s): Osamu Takeuchi
  • Organizer: Toll2011
  • Place of Presentation: Riva del Garda, Italy
• [Presentation] Zc3h12a, an RNase promoting Interleukin 6 mRNA decay, undergoes posttranscriptional modification to pathogenic stimuli (2011)
  • Author(s): Osamu Takeuchi
  • Organizer: RNA2011
  • Place of Presentation: 国立京都国際会館(京都)(招待講演)
• [Presentation] Mechanisms of innate immune recognition to virus infection (2010)
  • Author(s): Osamu Takeuchi
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: パシフィコ横浜(神奈川)(招待講演)
  • Year and Date: 2010-12-09
• [Presentation] RIG-Iファミリーによるウイルス感染認識メカニズム (2010)
  • Author(s): 竹内理
  • Organizer: 第58回日本ウイルス学会
  • Place of Presentation: あわぎんホール(徳島)(招待講演)
  • Year and Date: 2010-11-09
• [Presentation] 自然免疫たよる炎症制御機構 (2010)
  • Author(s): 竹内理
  • Organizer: Molecular Cardiovascular Conference II
  • Place of Presentation: キロロ ホテルピアノ(北海道)(招待講演)
  • Year and Date: 2010-09-03
• [Presentation] Role of Zc3h12c in regulating inflammatory responses in macrophages (2010)
  • Author(s): Osamu Takeuchi
  • Organizer: International Congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル(兵庫)
  • Year and Date: 2010-08-23
• [Presentation] Zc3h12a is an RNase promoting Interleukin 6 mRNA decay and regulates immune responses. (2010)
  • Author(s): Osamu Takeuchi
  • Organizer: Gordon Conference
  • Place of Presentation: Salve Regina University (USA)(招待講演)
• [Remarks] ホームページ
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• [Remarks]
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• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/Takeuchi_HP/index.html
• [Remarks]
  • URL: http://hostdefense.ifrec.osaka-u.ac.jp/ja/index.html