The role of TYK2 in the modulation of inflammatory responses

• Project/Area Number: 25460056
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: MUROMOTO Ryuta 北海道大学, 薬学研究科(研究院), 助教 (30455597)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: TYK2 / 炎症 / サイトカイン / 乾癬 / ケモカイン / マクロファージ / ケラチノサイト

Outline of Final Research Achievements

We aimed to investigate the role of Tyrosine kinase 2 (TYK2) in the modulation of inflammatory responses. We have found that TYK2 is involved in maintaining the basal expression of chemokine mRNAs in macrophages and in IL-17A-induced activation of keratinocytes. These findings suggest that TYK2 inhibition may be useful as a therapeutic strategy for treating immune-mediated inflammatory diseases such as psoriasis.

Research Products

• [Journal Article] Caspase-dependent cleavage regulates protein levels of Epstein-Barr virus-derived latent membrane protein 1. (2016)
  • Author(s): Togi S, Hatano Y, Muromoto R, Kawanishi E, Ikeda O, Hirashima K, Kon S, Kitai Y, Yasui T, Oritani K, Matsuda T.
  • Journal Title: FEBS Lett. Volume: 590 Issue: 6 Pages: 808-818
  • DOI: 10.1002/1873-3468.12119
  • NAID: 120005981517
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-17A plays a central role in the expression of psoriasis signature genes through the induction of IkB-delta in keratinocytes. (2016)
  • Author(s): Ryuta Muromoto, Toru Hirao, Keisuke Tawa, Koki Hirashima, Shigeyuki Kon, Yuichi Kitai, Tadashi Matsuda
  • Journal Title: Int. Immunol. Volume: in press Issue: 9 Pages: 443-452
  • DOI: 10.1093/intimm/dxw011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A new STAT3-binding partner, ARL3, enhances the phosphorylation and nuclear accumulation of STAT3. (2016)
  • Author(s): Togi S, Muromoto R, Hirashima K, Kitai Y, Okayama T, Ikeda O, Matsumoto N, Kon S, Sekine Y, Oritani K, Matsuda T.
  • Journal Title: J Biol Chem. Volume: 印刷中 Issue: 21 Pages: 11161-11171
  • DOI: 10.1074/jbc.m116.724849
  • NAID: 120006219975
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PML suppresses IL-6-induced STAT3 activation by interfering with STAT3 and HDAC3 interaction. (2015)
  • Author(s): Masaya Kato, Ryuta Muromoto, Sumihito Togi, Masashi Iwakami, Yuichi Kitai, Shigeyuki Kon, Kenji Oritani, and Tadashi Matsuda
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 461 Issue: 2 Pages: 366-371
  • DOI: 10.1016/j.bbrc.2015.04.040
  • NAID: 120005906774
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body. (2015)
  • Author(s): Sekine Y, Togi S, Muromoto R, Kon S, Kitai Y, Yoshimura A, Oritani K, Matsuda T.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 28 Pages: 17462-17473
  • DOI: 10.1074/jbc.m115.658575
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities. (2015)
  • Author(s): Togi S, Nakasuji M, Muromoto R, Ikeda O, Okabe K, Kitai Y, Kon S, Oritani K, Matsuda T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 3 Pages: 395-400
  • DOI: 10.1016/j.bbrc.2015.05.080
  • NAID: 120005820702
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CCR7 is involved in BCR-ABL/STAP-2-mediated cell growth in hematopoietic Ba/F3 cells. (2015)
  • Author(s): Kubo K, Iwakami M, Muromoto R, Inagaki T, Kitai Y, Kon S, Sekine Y, Oritani K, Matsuda T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 463 Issue: 4 Pages: 825-831
  • DOI: 10.1016/j.bbrc.2015.06.020
  • NAID: 120005822514
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isoflavones enhance interleukin-17 gene expression via retinoic acid receptor-related orphan receptors alpha and gamma. (2015)
  • Author(s): Hiroyuki Kojima, Yukimasa Takeda, Ryuta Muromoto, Miki Takahashi, Toru Hirao, Shinji Takeuchi, Anton M Jetten, and Tadashi Matsuda
  • Journal Title: Toxicology Volume: 329 Pages: 32-39
  • DOI: 10.1016/j.tox.2015.01.007
  • NAID: 120005712473
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis. (2014)
  • Author(s): Fujita N, Oritani K, Ichii M, Yokota T, Saitoh N, Okuzaki D, Sekine Y, Kon S, Muromoto R, Saitoh K, Yoshimura A, Matsuda T, Kanakura Y.
  • Journal Title: Eur J Immunol. Volume: 44 Issue: 6 Pages: 1791-1801
  • DOI: 10.1002/eji.201344239
  • Peer Reviewed / Open Access
• [Journal Article] The novel α4B murine α4 integrin splicing variant inhibits α4-dependent cell adhesion. (2014)
  • Author(s): Kouro H, Kon S, Matsumoto N, Miyashita T, Kakuchi A, Ashitomi D, Saito K, Nakatsuru T, Togi S, Muromoto R, Matsuda T.
  • Journal Title: J Biol Chem. Volume: 289 Issue: 23 Pages: 16389-16398
  • DOI: 10.1074/jbc.m114.553610
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tyk2 is a therapeutic target for psoriasis-like skin inflammation. (2014)
  • Author(s): Ishizaki M, Muromoto R, Akimoto T, Sekine Y, Kon S, Diwan M, Maeda, H, Togi S, Shimoda K, Oritani K, Matsuda T.
  • Journal Title: Int. Immunol. Volume: 26 Issue: 5 Pages: 257-267
  • DOI: 10.1093/intimm/dxt062
  • NAID: 120005522324
  • Peer Reviewed
• [Journal Article] Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses. (2014)
  • Author(s): Sekine Y, Nishida K, Yamasaki S, Muromoto R, Kon S, Kashiwakura J, Saitoh K, Togi S, Yoshimura A, Oritani K, Matsuda T
  • Journal Title: J Immunol Volume: 192 Issue: 8 Pages: 3488-3495
  • DOI: 10.4049/jimmunol.1300886
  • Peer Reviewed
• [Journal Article] Y14 positively regulates TNF-α-induced NF-κB transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein. (2013)
  • Author(s): Togi S, Shiga K, Muromoto R, Kato M, Souma Y, Sekine Y, Kon S, Oritani K, Matsuda T.
  • Journal Title: J Immunol Volume: 191 Issue: 3 Pages: 1436-1444
  • DOI: 10.4049/jimmunol.1300501
  • Peer Reviewed
• [Journal Article] Jun activation domain-binding protein 1 (JAB1) is required for the optimal response to interferons. (2013)
  • Author(s): Muromoto R, Nakajima M, Hirashima K, Hirao T, Kon S, Shimoda K, Oritani K, Matsuda T.
  • Journal Title: J Biol Chem Volume: 288 Issue: 43 Pages: 30969-30979
  • DOI: 10.1074/jbc.m113.485847
  • NAID: 120005397865
  • Peer Reviewed
• [Presentation] ケラチノサイトのIL-17応答におけるTYK2による間接的制御 (2016)
  • Author(s): 室本竜太、多和佳佑、松田正
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-03-27
• [Presentation] Interleukin-17A plays a fundamental role in the expression of psoriasis signature genes in keratinocytes through the induction of IkappaB-zeta (2015)
  • Author(s): Ryuta Muromoto, Toru Hirao, Keisuke Tawa and Tadashi Matsuda
  • Organizer: 日本研究皮膚科学会 第40回年次学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター（岡山県・岡山市）
  • Year and Date: 2015-12-11
• [Presentation] The role of TYK2 in IL-17A-incuded keratinocyte response (2015)
  • Author(s): MUROMOTO Ryuta and MATSUDA Tadashi
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Tyk2 mediates induction of CXCR3 ligands during imiquimod-induced psoriasis-like skin inflammation (2015)
  • Author(s): HIRASHIMA Koki, MUROMOTO Ryuta and MATSUDA Tadashi
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-18
• [Presentation] 炎症性サイトカイン刺激による角化細胞の活性化とIL-17A特異的なシグナルの解析 (2015)
  • Author(s): 平尾徹、室本竜太、松田正
  • Organizer: 日本薬学会北海道支部第142回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-05-16
• [Presentation] ケラチノサイトにおけるIL-17AシグナルへのTYK2の関与 (2015)
  • Author(s): 多和佳祐、室本竜太、松田正
  • Organizer: 日本薬学会北海道支部第142回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-05-16
• [Presentation] 造血系腫瘍における形質変化とSTAP-2の役割 (2015)
  • Author(s): 稲垣拓也、岩上昌史、久保果央莉、室本竜太、今重之、松田正
  • Organizer: 日本薬学会北海道支部第142回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-05-16
• [Presentation] マクロファージの脂質代謝系制御におけるTyrosine kinase 2 (TYK2)の関与 (2015)
  • Author(s): 平島洸基、室本竜太、松田正
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 兵庫医療大学（神戸市）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ケラチノサイトのIL-17応答調節におけるJAKファミリーチロシンキナーゼの役割 (2015)
  • Author(s): 多和佳佑、室本竜太、松田正
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 兵庫医療大学（神戸市）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Elucidation of unique and clinically meaningful IL-17-driven signaling pathway in keratinocytes (2014)
  • Author(s): Muromoto Ryuta, Matsuda Tadashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Caspase-dependent regulation of theprotein level of Epstein-Barr virus-derived latent membrane protein 1 (2014)
  • Author(s): HATANO Yosuke, TOGI Sumihito, MUROMOTO Ryuta, KON Shigeyuki, ORITANI Kenji, MATSUDA Tadashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] NEDD8化によるインターフェロン応答の調節 (2014)
  • Author(s): 室本竜太、中島麻衣子、平島洸基、平尾徹、今重之、下田和哉、織谷健司、松田正
  • Organizer: 第79回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北海道大学医学部学友会館「フラテ」（札幌市）
  • Year and Date: 2014-06-19
• [Presentation] マクロファージのCXCL10産生におけるTyk2関与の分子機構の解析 (2014)
  • Author(s): 平島洸基、室本竜太、大城裕也、松田正
  • Organizer: 日本薬学会北海道支部第141回例会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2014-05-24
• [Presentation] Jun activation domain-binding protein 1 (JAB1)/CSN5 is required for the optimal response to interferon-alpha. (2013)
  • Author(s): Ryuta Muromoto and Tadashi Matsuda
  • Organizer: IMMUNOLOGY 2013 The American Association of Immunologists AAI Annual Meeting
  • Place of Presentation: Hawaii Convention Center, Honolulu, Hawaii
• [Presentation] マクロファージ由来ケモカイン発現におけるTyk2関与の分子機構の解析 (2013)
  • Author(s): 平島洸基、室本竜太、大城裕也、相馬悠樹、松田正
  • Organizer: 第36回分子生物学会年会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] A role of neddylation in regulating interferon responses. (2013)
  • Author(s): Ryuta Muromoto and Tadashi Matsuda
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] STAP-2 cooperates with BCR-ABL to modify the expression of chemokine receptors (2013)
  • Author(s): IWAKAMI Masashi, MUROMOTO Ryuta, SEKINE Yuichi, KON Shigeyuki, ORITANI Kenji, MATSUDA Tadashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] Y14 positively regulates TNF-α induced NF-κB transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein (2013)
  • Author(s): TOGI Sumihito, MUROMOTO Ryuta, KON Shigeyuki, ORITANI Kenji, MATSUDA Tadashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Remarks] 北海道大学薬学部ホームページ
  • URL: http://www.pharm.hokudai.ac.jp/