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Characterization of multifunctional roles of TRAF5 in pro-inflammatory cytokine receptor signaling

Research Project

Project/Area Number 18H02572
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionUniversity of Toyama

Principal Investigator

SO Takanori  富山大学, 学術研究部薬学・和漢系, 教授 (60294964)

Co-Investigator(Kenkyū-buntansha) 守田 雅志  富山大学, 学術研究部薬学・和漢系, 准教授 (20191033)
石井 直人  東北大学, 医学系研究科, 教授 (60291267)
川口 甲介  富山大学, 学術研究部薬学・和漢系, 助教 (80624866)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords免疫 / 炎症 / サイトカイン / TRAF / シグナル伝達
Outline of Final Research Achievements

In this study, we found novel roles of TRAF5 in immunity and inflammation: 1) negative regulatory function of TRAF5 in signaling mediated by receptors for IL-6 and IL-27, 2) significance of TRAF5 in differentiation and effector function of plasmacytoid dendritic cells, 3) inflammatory function of TRAF5 in lung inflammation mediated by OSM, 4) inflammatory function of TRAF5 in colonic inflammation mediated by DSS. These results indicate that TRAF5 expressed by different cell types controls inflammatory signaling in both positive and negative ways. Further study is essential to understand the regulatory roles of TRAF5 and its family molecules in health and diseases.

Academic Significance and Societal Importance of the Research Achievements

老化により炎症性疾患の頻度が増加することから、その根底に存在する炎症のしくみを理解することは、超高齢社会を迎えた日本で非常に重要な課題である。炎症応答で体内の様々な細胞から産生される代表的な炎症性サイトカインTNF、IL-6、IL-1とこれらのファミリー分子群の作用は、炎症性疾患の病態と密接に関連する。本研究で、TRAF5がIL-6、IL-27、OSM、TNF-αの受容体やTLRのシグナル伝達に関連することで、炎症や免疫応答を制御する新しい機序を明らかにした。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 10 results) Presentation (13 results) Book (1 results)

  • [Journal Article] Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice2021

    • Author(s)
      Morita Masashi、Kaizawa Taro、Yoda Taiki、Oyama Takuro、Asakura Reina、Matsumoto Shun、Nagai Yoshinori、Watanabe Yasuharu、Watanabe Shiro、Kobayashi Hiroshi、Kawaguchi Kosuke、Yamamoto Seiji、Shimozawa Nobuyuki、So Takanori、Imanaka Tsuneo
    • Journal Title

      Journal of Inherited Metabolic Disease

      Volume: 44 Issue: 3 Pages: 718-727

    • DOI

      10.1002/jimd.12346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acyl-CoA thioesterase activity of peroxisomal ABC protein ABCD1 is required for the transport of very long-chain acyl-CoA into peroxisomes2021

    • Author(s)
      Kawaguchi Kosuke、Mukai Emi、Watanabe Shiro、Yamashita Atsushi、Morita Masashi、So Takanori、Imanaka Tsuneo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 2192-2192

    • DOI

      10.1038/s41598-021-81949-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of an immortalized astrocytic cell line from Abcd1-deficient H-2KbtsA58 mice to facilitate the study of the role of astrocytes in X-linked adrenoleukodystrophy2021

    • Author(s)
      Morita Masashi、Toida Ai、Horiuchi Yuki、Watanabe Shiro、Sasahara Masakiyo、Kawaguchi Kosuke、So Takanori、Imanaka Tsuneo
    • Journal Title

      Heliyon

      Volume: 7 Issue: 2 Pages: e06228-e06228

    • DOI

      10.1016/j.heliyon.2021.e06228

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Analysis of the Transcriptional Regulator IκB-ζ in Intestinal Homeostasis2021

    • Author(s)
      Sasaki Tomoki、Nagashima Hiroyuki、Okuma Atsushi、Yamauchi Takeshi、Yamasaki Kenshi、Aiba Setsuya、So Takanori、Ishii Naoto、Owada Yuji、MaruYama Takashi、Kobayashi Shuhei
    • Journal Title

      Digestive Diseases and Sciences

      Volume: - Issue: 4 Pages: 1252-1259

    • DOI

      10.1007/s10620-021-06958-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The lysosomal protein ABCD4 can transport vitamin B12 across liposomal membranes in?vitro2021

    • Author(s)
      Kitai Katsuki、Kawaguchi Kosuke、Tomohiro Takenori、Morita Masashi、So Takanori、Imanaka Tsuneo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100654-100654

    • DOI

      10.1016/j.jbc.2021.100654

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GITR controls intestinal inflammation by suppressing IL-15-dependent NK cell activity.2020

    • Author(s)
      Sakurai T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Kawabe T, Ndhlovu LC, Riccardi C, Kudo H, Wada M, Nio M, So T, Ishii N.
    • Journal Title

      FASEB J.

      Volume: 34(11) Issue: 11 Pages: 14820-14831

    • DOI

      10.1096/fj.202001675r

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TRAF5 promotes plasmacytoid dendritic cell development from bone marrow progenitors2020

    • Author(s)
      Kobayashi Shuhei、Shiota Yuka、Kawabe Takeshi、Phung Hai The、Maruyama Takashi、Owada Yuji、So Takanori、Ishii Naoto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 521 Issue: 2 Pages: 353-359

    • DOI

      10.1016/j.bbrc.2019.10.123

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells2020

    • Author(s)
      Phung Hai The、Nagashima Hiroyuki、Kobayashi Shuhei、Asano Naoki、Machiyama Tomoaki、Sakurai Tsuyoshi、Tayama Shun-ichi、Asao Atsuko、Imatani Akira、Kawabe Takeshi、Okuyama Yuko、Ishii Naoto、So Takanori
    • Journal Title

      ImmunoHorizons

      Volume: 4 Issue: 3 Pages: 129-139

    • DOI

      10.4049/immunohorizons.2000007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TNF Receptor-Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression2019

    • Author(s)
      Kobayashi Shuhei、Sakurai Tsuyoshi、So Takanori、Shiota Yuka、Asao Atsuko、Phung Hai The、Tanaka Riou、Kawabe Takeshi、Maruyama Takashi、Kanno Emi、Kawakami Kazuyoshi、Owada Yuji、Ishii Naoto
    • Journal Title

      The Journal of Immunology

      Volume: 203 Issue: 6 Pages: 1447-1456

    • DOI

      10.4049/jimmunol.1900188

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s2019

    • Author(s)
      Tayama Shunichi、Okuyama Yuko、Phung Hai The、Asao Atsuko、Kobayashi Shuhei、Musha Tomomi、Machiyama Tomoaki、Sakurai Tsuyoshi、Zhang Chengming、Ushio-Fukai Masuko、Kawabe Takeshi、So Takanori、Ishii Naoto
    • Journal Title

      International Immunology

      Volume: - Issue: 4 Pages: 233-241

    • DOI

      10.1093/intimm/dxz077

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IQGAP1 restrains T‐cell cosignaling mediated by OX402019

    • Author(s)
      Okuyama Yuko、Nagashima Hiroyuki、Ushio‐Fukai Masuko、Croft Michael、Ishii Naoto、So Takanori
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 1 Pages: 540-554

    • DOI

      10.1096/fj.201900879rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome2019

    • Author(s)
      Niitsuma Sou、Kudo Hiroki、Kikuchi Atsuo、Hayashi Takaya、Kumakura Satoshi、Kobayashi Shuhei、Okuyama Yuko、Kumagai Naonori、Niihori Tetsuya、Aoki Yoko、So Takanori、Funayama Ryo、Nakayama Keiko、Shirota Matsuyuki、Kondo Shuji、Kagami Shoji、Tsukaguchi Hiroyasu、Iijima Kazumoto、Kure Shigeo、Ishii Naoto
    • Journal Title

      International Immunology

      Volume: 32 Issue: 4 Pages: 283-292

    • DOI

      10.1093/intimm/dxz081

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GITR cosignal in ILC2s controls allergic lung inflammation.2018

    • Author(s)
      Nagashima H, Okuyama Y, Fujita T, Takeda T, Motomura Y, Moro K, Hidaka T, Omori K, Sakurai T, Machiyama T, Ndhlovu LC, Riccardi C, So T, Ishii N.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: - Issue: 5 Pages: 1939-1943.e8

    • DOI

      10.1016/j.jaci.2018.01.028

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.2018

    • Author(s)
      Machiyama T, So T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Harigae H, Ishii N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: - Issue: 3 Pages: 544-550

    • DOI

      10.1016/j.bbrc.2018.03.186

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRAF2 and TRAF5 associated with the signal transducing receptor gp130 limit IL-6-driven transphosphorylation of JAK1 through the inhibition of proximal JAK-JAK interaction.2018

    • Author(s)
      Kimura M, Nagashima H, Okuyama Y, Ishii N, and So T
    • Journal Title

      Int. Immunol

      Volume: - Issue: 7 Pages: 219-299

    • DOI

      10.1093/intimm/dxy029

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Interleukin-6 Receptor Signaling by TNF Receptor-Associated Factor 2 and 5 During Differentiation of Inflammatory CD4+ T Cells2018

    • Author(s)
      Nagashima Hiroyuki、Ishii Naoto、So Takanori
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1986-1986

    • DOI

      10.3389/fimmu.2018.01986

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] TRAF5 による CD4+ T 細胞の IL-27 受容体シグナル調節機構2021

    • Author(s)
      河原 永悟,藤森 由夏,大石 真結,川口 甲介,守田 雅志,奥山 祐子,石井 直人,宗 孝紀
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] TNF 受容体の細胞内領域に含まれるTRAF 結合ペプチドモチーフの精密化を目指した研究2019

    • Author(s)
      飯田日向子,帯田孝之,宗孝紀,水口峰之
    • Organizer
      日本薬学会北陸支部第131回例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CD4陽性T細胞のIL-27受容体シグナルにおけるTRAF5の抑制性機能の解明2019

    • Author(s)
      河原永悟,藤森由夏,大石真結,川口甲介,守田雅志,奥山祐子,石井直人,宗孝紀
    • Organizer
      日本薬学会北陸支部第131回例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] サイトカイン受容体 gp130 と TRAF タンパク質の相互作用様式の解明2019

    • Author(s)
      藤森由夏,河原永悟,川口甲介,守田雅志,帯田孝之,奥山祐子,水口峰之,石井直人,宗孝紀
    • Organizer
      日本薬学会北陸支部第131回例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TNFR-associated factor (TRAF) 5 expressed by intestinal epithelial cells promotes NF-kB-mediated inflammation via controlling TRAF2 stability in dextran sulfate sodium-induced colitis2019

    • Author(s)
      Phung HT, Nagashima H, Kobayashi S, Machiyama T, Sakurai T, Tayama S, Asao A, Okuyama Y, Ishii N, So T
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] IQGAP1 regulates ILC2 apoptosis in the lung2019

    • Author(s)
      Tayama S, Okuyama Y, Phung HT, Kawabe T, So T, Ishii N
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Understanding the role of TRAF family proteins in gp130 signaling2019

    • Author(s)
      Fujimori Y, Kawahara E, Morita M, Okuyama Y, Ishii N, So T
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TNF receptor-associated factor 5 inhibits IL-27 receptor signaling in CD4+ T-lymphocytes2019

    • Author(s)
      Kawahara E, Fujimori Y, Oishi M, Morita M, Ishii N, Okuyama Y, So T
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GITR signaling negatively controls DSS-induced intestinal inflammation by regulating NK cells function2019

    • Author(s)
      Sakurai T, Okuyama Y, Hai Phung HT, So T, Nio M, Ishii N
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GITR co-signaling controls group 2 innate lymphoid cells through IL-9 induction in allergic lung inflammation.2018

    • Author(s)
      Okuyama Y, Nagashima H, Motomura Y, Moro K, Sakurai T, Ndhlovu LC, Riccardi C, So T, Ishii N.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Functional regulation of plasmacytoid dendritic cells by TNF receptor associated factor 5.2018

    • Author(s)
      Kobayashi S, Sakurai T, Asao A, Phung HT, So T, Ishii N.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.2018

    • Author(s)
      Machiyama T, So T, Harigae H, Ishii N.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] TRAF5 maintains the expression level of TRAF2 in nonhematopoietic cells and exacerbates DSS-colitis in mice.2018

    • Author(s)
      Phung HT, Nagashima H, Kobayashi S, Machiyama T, Asao A, Okuyama Y, Ishii N, So T.
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Book] Co-signal Molecules in T Cell Activation2019

    • Author(s)
      So Takanori、Ishii Naoto
    • Total Pages
      32
    • Publisher
      Springer
    • ISBN
      9789813297166
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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