Regulatory Mechanisms of the Balance between Inflammation andAnti-inflammation by Cutokines

• Project/Area Number: 22249009
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Keio University
• Principal Investigator: YOSHIMURA Akihiko 慶應義塾大学, 医学部, 教授 (90182815)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000); Fiscal Year 2012: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2011: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
• Keywords: サイトカイン / シグナル伝達 / チロシンキナーゼ / 転写因子 / ヘルパーT細胞 / 抑制性T細胞 / TGF-β / 炎症 / 免疫応答 / 自己免疫疾患 / TGFーβ / Foxp3 / 胸腺 / TGFβ / RORgammat / インターフェロン / SOCS / アレルギー / STAT

Research Abstract

Cytokines play essential roles in regulation of innate and adaptive immunity. The transforming growthfactor-E (TGF-E) has been shown to play pivotal roles in T-cell homeostasis, Th17 and Tregdifferentiation, and immune suppression. In this study, we demon

Research Products

• [Journal Article] Nr4a receptors areessential for thymic regulatory T cell developmentand immune homeostasis. (2013)
  • Author(s): Sekiya T, Kashiwagi I, Yoshida R, Fukaya T,Morita R, Kimura A, Ichinose H, Metzger D,Chambon P, Yoshimura A
  • Journal Title: Nature Immunol. Volume: 14(3) Pages: 230-7
  • Peer Reviewed
• [Journal Article] IL-23-Independent Induction of IL-17 from γδTCells and Innate Lymphoid Cells PromotesExperimental Intraocular Neovascularization (2013)
  • Author(s): Hasegawa E, Sonoda KH, Shichita T, Morita R,Sekiya T, Kimura A, Oshima Y, Takeda A,Yoshimura T, Yoshida S, Ishibashi T, Yoshimura A.
  • Journal Title: JImmunol. Volume: 190(4) Pages: 1778-87
  • Peer Reviewed
• [Journal Article] Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. (2013)
  • Author(s): Sekiya T, Kashiwagi I, Yoshida R, Fukaya T, et al.
  • Journal Title: Nat Immunol. Volume: 14 Issue: 3 Pages: 230-237
  • DOI: 10.1038/ni.2520
  • Peer Reviewed
• [Journal Article] IL-23-Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization (2013)
  • Author(s): Hasegawa E
  • Journal Title: J Immunol Volume: 190 Issue: 4 Pages: 1778-1787
  • DOI: 10.4049/jimmunol.1202495
  • Peer Reviewed
• [Journal Article] Peroxiredoxin familyproteins are key initiators of post-ischemicinflammation in the brain (2012)
  • Author(s): Shichita T, Hasegawa E, Kimura A, MoritaR,Sakaguchi R, Takada I, Sekiya T, Ooboshi H,Kitazono T, Yanagawa T, Ishii T, TakahashiH, Mori S, Nishibori M, Kuroda K, Akira S,Miyake K, and Yoshimura A
  • Journal Title: Nature Medicine Volume: 18(6) Pages: 911-7
  • Peer Reviewed
• [Journal Article] protein-2 modulates fas-mediated T cell apoptosisby interacting with caspase-8 (2012)
  • Author(s): Sekine Y, Yamamoto C, Kakisaka M, MuromotoR, Kon S, Ashitomi D, Fujita N, Yoshimura A,Oritani K, Matsuda T. Signal-transducing adap
  • Journal Title: J Immunol Volume: 188(12) Pages: 6194-204
  • Peer Reviewed
• [Journal Article] Smad2 and Smad3 are redundantlyessential for the suppression of iNOS synthesis inmacrophages by regulating IRF3 and STAT1pathways. (2012)
  • Author(s): Sugiyama Y, Kakoi K, Kimura A, Takada I,Kashiwagi I, Wakabayashi Y, Morita R, Nomura M,Yoshimura A
  • Journal Title: Int Immunol. Volume: 24(4) Pages: 253-65
  • Peer Reviewed
• [Journal Article] CCL2-Induced Migration andSOCS3-Mediated Activation of Macrophages AreInvolved in Cerulein-Induced Pancreatitis in Mice (2012)
  • Author(s): Saeki K, Kanai T, Nakano M, Nakamura Y,Miyata N, Sujino T, Yamagishi Y, Ebinuma H,Takaishi H, Ono Y, Takeda K, Hozawa S,Yoshimura A, Hibi T
  • Journal Title: Gastroenterology Volume: 142(4) Pages: 1010-1020
  • Peer Reviewed
• [Journal Article] Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain (2012)
  • Author(s): Shichita T
  • Journal Title: Nature Medicine Volume: 18 Issue: 6 Pages: 911-917
  • DOI: 10.1038/nm.2749
  • Peer Reviewed
• [Journal Article] The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells (2011)
  • Author(s): Sekiya, T., et al
  • Journal Title: Nature Communications Volume: 2 Issue: 1 Pages: 269-269
  • DOI: 10.1038/ncomms1272
  • Peer Reviewed
• [Journal Article] Transcription Factor Smad-Independent T Helper 17 Cell Inductionby Transforming-Growth Factor-β Is Mediatedby Suppression of Eomesodermin (2011)
  • Author(s): Ichiyama K, Sekiya T, Inoue N, Tamiya T,Kashiwagi I, Kimura A, Morita R, Muto G, ShichitaT, Takahashi R, Yoshimura A.
  • Journal Title: Immunity Volume: 27;34(5) Pages: 741-54
  • Peer Reviewed
• [Journal Article] miR126 positivelyregulates mast cell proliferation and cytokineproduction through suppressing Spred1 (2011)
  • Author(s): Ishizaki T, Tamiya T, Taniguchi K, Morita R,Kato R, Okamoto F, Saeki K, Nomura M,Nojima Y, Yoshimura A.
  • Journal Title: GenesCells. Volume: 16(7) Pages: 803-814
  • Peer Reviewed
• [Journal Article] SOCS1 is essential forregulatory T cell functions by preventing loss ofFoxp3 expression as well as IFN-{gamma} andIL-17A production. (2011)
  • Author(s): Takahashi R, Nishimoto S, Muto G, Sekiya T,Tamiya T, Kimura A, Morita R, Asakawa M,Chinen T, Yoshimura A.
  • Journal Title: J Exp Med Volume: 208(10) Pages: 2055-67
  • Peer Reviewed
• [Journal Article] Desmoglein 3-specific CD4+ T cellsinduce pemphigus vulgaris and interfacedermatitis in mice. (2011)
  • Author(s): Takahashi H, Kouno M, Nagao K, Wada N,Hata T, Nishimoto S, Iwakura Y, Yoshimura A,Yamada T, Kuwana M, Fujii H, Koyasu S,Amagai M
  • Journal Title: J Clin Invest Volume: 121(9) Pages: 3677-88
  • Peer Reviewed
• [Journal Article] 1,25-dihydroxyvitamin D(3) ameliorates Th17autoimmunity via transcriptional modulation ofinterleukin-17A (2011)
  • Author(s): Joshi S, Pantalena LC, Liu XK, Gaffen SL, LiuH, Rohowsky-Kochan C, Ichiyama K, YoshimuraA, Steinman L, Christakos S, Youssef S
  • Journal Title: Mol Cell Biol. Volume: 31(17) Pages: 3653-69
  • Peer Reviewed
• [Journal Article] Histone 3 lysine 9 (H3K9) methyltransferaserecruitment to the interleukin-2 (IL-2) promoter isa mechanism of suppression of IL-2 transcriptionby the transforming growth factor-β-Smadpathway. (2011)
  • Author(s): Wakabayashi Y, Tamiya T, Takada I, Fukaya T,Sugiyama Y, Inoue N, Kimura A, Morita R,Kashiwagi I, Takimoto T, Nomura M, YoshimuraA.
  • Journal Title: J Biol Chem. Volume: 286(41) Pages: 35456-65
  • Peer Reviewed
• [Journal Article] Pyridone 6, a pan-JAK inhibitor,ameliorates allergic skin inflammation of NC/Ngamice via suppression of Th2 and enhancement ofTh17. (2011)
  • Author(s): Nakagawa R, Yoshida H, Asakawa M, TamiyaT, Inoue N, Morita R, Inoue H, Nakao A,Yoshimura A.
  • Journal Title: J Immunol. Volume: 187(9) Pages: 4611-20
  • Peer Reviewed
• [Journal Article] Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-ss Is Mediated by Suppression of Eomesodermin (2011)
  • Author(s): Kenji Ichiyama, 他
  • Journal Title: Immunity Volume: 34 Issue: 5 Pages: 741-754
  • DOI: 10.1016/j.immuni.2011.02.021
  • Peer Reviewed
• [Journal Article] Pyridone 6, a pan-JAK inhibitor, ameliorates allergic skin inflammation of NC/Nga mice via suppression of Th2 and enhancement of Th17 (2011)
  • Author(s): Ryusuke Nakagawa, 他
  • Journal Title: Journal of Immunology Volume: 187 Issue: 9 Pages: 4611-4620
  • DOI: 10.4049/jimmunol.1100649
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. (2011)
  • Author(s): Chinen T, Komai K, Muto G Yoshimura A, et al.
  • Journal Title: Nature Communications Volume: 2
  • Peer Reviewed
• [Journal Article] The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4(+) T cells. (2011)
  • Author(s): Sekiya T, Kashiwagi I, Inoue N, Yoshimura A, et al.
  • Journal Title: Nature Communications Volume: 2
  • Peer Reviewed
• [Journal Article] Smad2 and Smad3 are redundantly essential forthe TGF-beta-mediated regulation of regulatoryT plasticity and Th1 development. (2010)
  • Author(s): Takimoto T, Wakabayashi Y, Sekiya T, InoueN, Morita R, Ichiyama K, Takahashi R,Asakawa M, Muto G, Mori T, Hasegawa E,Shizuya S, Hara T, Nomura M, Yoshimura A
  • Journal Title: J Immunol. Volume: 185(2) Pages: 842-55
  • Peer Reviewed
• [Journal Article] Function ofmiR-146a in controlling Treg cell-mediatedregulation of Th1 responses. (2010)
  • Author(s): Lu LF, Boldin MP, Chaudhry A, Lin LL,Taganov KD, Hanada T, Yoshimura A,Baltimore D, Rudensky AY
  • Journal Title: Cell. Volume: 142(6) Pages: 914-29
  • Peer Reviewed
• [Journal Article] Suppressors of cytokinesignaling 3 inhibits LPS-induced IL-6 expressionin osteoblasts by suppressingCCAAT/enhancer-binding protein {beta} activity (2010)
  • Author(s): Yan C, Cao J, Wu M, Zhang W, Jiang T,Yoshimura A, Gao H.
  • Journal Title: J Biol Chem. Volume: 285(48) Pages: 37227-39
  • Peer Reviewed
• [Journal Article] Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. (2010)
  • Author(s): Takimoto T, Wakabayashi Y, Sekiya T, Yoshimura A, et al
  • Journal Title: J Immunol. Volume: 185(7) Pages: 842-855
  • Peer Reviewed
• [Presentation] The nuclear orphan receptor Nr4a family isessential for nTreg development and immunehomeostasis (2013)
  • Author(s): YOSHIMURA Akihiko and SEKIYA Takashi
  • Organizer: JST-CREST Symposium"Frontiers in Immunology and Inflammation"
  • Place of Presentation: Hitotsubashi Memorial Hall Tokyo
• [Presentation] Suppression of intestinalinflammation by signals of IL-10, TGF-beta andnovel factors (2013)
  • Author(s): Akihiko Yoshimura, Takatoshi Chinen andTakashi Sekiya
  • Organizer: keystone symposium Emerging Topics inImmune System Plasticity: Cellular Networks,Metabolic Control, and Regeneration.
  • Place of Presentation: Santa Fe, New Mexico, USA
• [Presentation] The IL-23-IL-17 axis inthe brain inflammation after stroke (2012)
  • Author(s): Akihiko Yoshimura
  • Organizer: The 34th Naito Conference
  • Place of Presentation: Chateraise Gateaux KingdomSAPPORO
• [Presentation] Suppression of intestinalinflammation by PGE2, IL-10 and SOCS1 (2012)
  • Author(s): Akihiko Yoshimura
  • Organizer: International Symposium on Immune Toleranceand Mucosal Immunology
  • Place of Presentation: Chengdu, China
• [Presentation] Molecular Bases for the Regulation of DC and T cell responses by TGF-β (2012)
  • Author(s): 吉村昭彦
  • Organizer: 第40会日本免疫学会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] The IL-23-IL-17 axis in the brain inflammation after stroke (2012)
  • Author(s): 吉村昭彦
  • Organizer: The 34th Naito Conference
  • Place of Presentation: 札幌
  • Invited
• [Presentation] Role of TGF-口eta-Smad2/3 signaling in helper Tcell function and differentiation (2011)
  • Author(s): Akihiko Yoshimura, Kenji Ichiyama
  • Organizer: 20thInternational Rheumatoid symposium
  • Place of Presentation: Kobe
  • Year and Date: 2011-07-19
• [Presentation] Regulation of innate immune tolerance by PGE2and SOCS1 in the intestine (2011)
  • Author(s): Akihiko Yoshimura, Tamiya Taiga, andTakatoshi Chinen
  • Organizer: Joint international meeting of JSICR-MMCB
  • Place of Presentation: Osaka
• [Presentation] Role of TGF-beta-Smad2/3 signaling in helper Tcell function and differentiation (2011)
  • Author(s): Akihiko Yoshimura, Kenji Ichiyama
  • Organizer: Keystone symposium "TGF-beta" Snowbird
  • Place of Presentation: USA
• [Presentation] T cell differentiation and cytokine network inimmunological diseases (2010)
  • Author(s): Akihiko Yo shimura
  • Organizer: 第19回国際リウマチシンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2010-04-23
• [Presentation] SOCS1 is necessary for innate immunetolerance to intestinal flora by regulatingprostaglandin- mediated immunosuppression (2010)
  • Author(s): Akihiko Yoshimura
  • Organizer: World Immune Regulation Meeeting -IVDavos
  • Place of Presentation: Switzerland.
  • Year and Date: 2010-04-01
• [Presentation] SOCS1 is necessary for innate immune tolerance to intestinal flora by regulating prostaglandin-mediated immunosuppression (2010)
  • Author(s): Akihiko Yoshimura
  • Organizer: World Immune Regulation Meeting-IV
  • Place of Presentation: Davos/Switzerland
  • Year and Date: 2010-04-01
• [Presentation] Role of IL-23 and IL-17-producing gdT cells inthe delayed phase of brain ischemia (2010)
  • Author(s): Akihiko Yoshimura, Takashi Shchita, FumieKonoeda
  • Organizer: China Treg/Th17
  • Place of Presentation: Shanghai China
• [Remarks]
  • URL: http://new.immunoreg.jp/
• [Remarks] 関谷君の論文がNature Immunologyに掲載されました。
  • URL: http://new.immunoreg.jp/modules/bulletin/index.php?page=article&storyid=62
• [Remarks] 長谷川君の論文がJ.Immunolに掲載されました
  • URL: http://new.immunoreg.jp/modules/bulletin/index.php?page=article&storyid=61
• [Remarks] 七田君の論文がNature Medicine 6月号に掲載
  • URL: http://new.immunoreg.jp/modules/bulletin/index.php?page=article&storyid=53
• [Remarks]
  • URL: http://new.immunoreg.jp/