Establishment of autoimmune disease therapies based on the elucidation of target genes

2012 Fiscal Year Final Research Report

• Project/Area Number: 20679005
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: YASUTOMO Koji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (30333511)
• Project Period (FY): 2008 – 2012
• Keywords: 自己免疫疾患 / T細胞 / ゲノム解析 / Notch

Research Abstract

We aim to reveal the molecular mechanisms to maintain immune homeostasis in order to establish therapeutic strategies for human immune-mediated disorders. We demonstrated the crucial roles of Notch signaling in cytotoxic T cellsresponses, IL-22 production from CD4+ T cells, the differentiation of macrophages in the small intestine and maintenance of memory T cells. Furthermore, we identified PSMB8 as a causative gene for a new type of autoinflammatory syndrome.

Research Products

• [Journal Article] The ARNT-STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+cells (2013)
  • Author(s): Nakajima K, Maekawa Y, KataokaK, IshifuneC, NishidaJ, ArimochiH, KitamuraA, YoshimotoT, TomitaS, NagahiroS, Yasutomo K
  • Journal Title: Nature Communications
  • Peer Reviewed
• [Journal Article] Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice (2012)
  • Author(s): ian G, Arimochi H, Kitamura A, Nishida J, Li S, Kishihara K, Maekawa Y, Yasutomo K
  • Journal Title: J Immunol Volume: 188 Pages: 2227-34
  • DOI: DOI:10.4049/jimmunol.1102586
  • Peer Reviewed
• [Journal Article] Notch2 regulates the development of marginal zone B cells through Fos (2012)
  • Author(s): Iwahashi S, Maekawa Y, Nishida J, Ishifune C, Kitamura A, Arimochi H, Kataoko K, Chiba S, Shimada M, Yasutomo K
  • Journal Title: iochem Biophys Res Commun Volume: 418 Pages: 701-707
  • DOI: DOI:10.1016/j.bbrc.2012.01.082
  • Peer Reviewed
• [Journal Article] Dll4-Fc, an inhibitor of Dll4-Notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-kappa-B activity. (2012)
  • Author(s): Kuramoto T, Goto H, Mitsuhashi A, Tabata S, Ogawa H, Uehara H, Sijo A, Kakiuchi S, Maekawa, Yasutomo K, Hanibuchi M, Akiyama SI, Sone S, Nishioka Y
  • Journal Title: Mol Cancer Ther Volume: 11 Pages: 2578-2587
  • DOI: DOI:10.1158/1535-7163.MCT-12-0640
  • Peer Reviewed
• [Journal Article] A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans (2011)
  • Author(s): Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K.
  • Journal Title: J Clin Invest Volume: 121 Pages: 4150-4160
  • DOI: DOI:10.1172/JCI58414
  • Peer Reviewed
• [Journal Article] Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production (2011)
  • Author(s): Xu M, Morishima N, Mizoguchi I, Chiba Y, Fujita K, Kuroda M, Iwakura Y, Cua DJ, Yasutomo K, Mizuguchi J, Yoshimoto T
  • Journal Title: Eur J Immunol Volume: 41 Pages: 2828-2839
  • DOI: DOI:10.1002/eji.201141291
  • Peer Reviewed
• [Journal Article] Low-dose lipopolysaccharide affects lung allergic responses by regulating Jagged1 expression on antigen-pulsed dendritic Cells. (2011)
  • Author(s): Okamoto M, Takeda K, Lucas JJ, Joetham A, Yasutomo K, Gelfand EW
  • Journal Title: Int Arch Allergy Immunol Volume: 157 Pages: 65-72
  • DOI: DOI:10.1159/000324836
  • Peer Reviewed
• [Journal Article] Notch signaling regulates the development of a novel type of Thy1-expressing dendritic cell in the thymus (2011)
  • Author(s): Ishifune C, Maekawa Y, Nishida J, Kitamura A, Tanigaki K, Yagita H, Yasutomo K
  • Journal Title: Eur J Immunol Volume: 41 Pages: 1309-1320
  • DOI: DOI:10.1002/eji.201041159
  • Peer Reviewed
• [Journal Article] Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine (2011)
  • Author(s): Sakata-Yanagimoto M, Sakai T, Miyake Y, Saito T, Maruyama H, Morishita Y, Nakagami-Yamaguchi E, Kumano K, Yagita H, Fukayama M, Ogawa S, Kurokawa M, Yasutomo K, Chiba S
  • Journal Title: Blood Volume: 117 Pages: 128-134
  • DOI: DOI:10.1182/blood-2010-07-289611
  • Peer Reviewed
• [Journal Article] Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. (2010)
  • Author(s): Alam MS, Maekawa Y, Kitamura A, Tanigaki K, Yoshimoto T, Kishihara K, Yasutomo K
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 5943-5948
  • DOI: DOI:10.1073/pnas.0911755107
  • Peer Reviewed
• [Journal Article] Notch2 signaling is required for potent anti-tumor immunity in vivo (2010)
  • Author(s): Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, Kojima H, Chiba S, Shimada M, Yasutomo K
  • Journal Title: J Immunol Volume: 184 Pages: 4673-4678
  • DOI: DOI:10.4049/jimmunol.0903661
  • Peer Reviewed
• [Journal Article] Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese (2010)
  • Author(s): Nishimoto K, Kochi Y, Ikari K, Yamamoto K, Suzuki A, Shimane K, Nakamura Y, Yano K, Iikuni N, Tsukahara S, Kamatani N, Okamoto H, Kaneko H, Kawaguchi Y, Hara M, Toyama Y, Horiuchi T, Tao K, Yasutomo K, Hamada D, Yasui N, Inoue H, Itakura M, Yamanaka H, Mo
  • Journal Title: Ann Rheum Dis Volume: 69 Pages: 368-373
  • DOI: DOI:10.1136/ard.2008.104315
  • Peer Reviewed
• [Journal Article] Gelfand EW. Jagged1 on dendritic cells and Notch on CD4+ T cells initiate lung allergic responsiveness by inducing IL-4 production. (2009)
  • Author(s): Okamoto M, Matsuda H, Lucas JL, Domenico J, Yasutomo K, Takeda K
  • Journal Title: J Immunol Volume: 183 Pages: 2995-3003
  • DOI: DOI:10.4049/jimmunol.0900692
  • Peer Reviewed
• [Journal Article] Notch activation induces the generation of functional natural killer cells from human cord blood CD34-positive cells devoid of interleukin-15. (2009)
  • Author(s): Haraguchi K, Suzuki T, Koyama N, Kumano K, Nakahara F, Matsumoto A, Yokoyama Y, Sakata-Yanagimoto M, Masuda S, Takahashi T, Kamijo A, Takahashi K, Takanashi M, Okuyama Y, Yasutomo K, Sakano S, Yagita H, Kurokawa M, Ogawa S, Chiba S.
  • Journal Title: J Immunol Volume: 182 Pages: 6168-6178
  • DOI: DOI:10.4049/jimmunol.0803036
  • Peer Reviewed
• [Journal Article] Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in CD8+ T cells. (2009)
  • Author(s): Kijima M, Iwata A, Maekawa Y, Uehara H, Izumi K, Kitamura A, Yagita H, Chiba S, Shiota H, Yasutomo K
  • Journal Title: J Immunol Volume: 182 Pages: 3566-3572
  • DOI: DOI:10.4049/jimmunol.0803765
  • Peer Reviewed
• [Journal Article] Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. (2005)
  • Author(s): Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Sakata-Yanagimoto M, Saito T, Taniuchi I, Chiba S, Sone S, Yasutomo K
  • Journal Title: Nature Immunology Volume: 9 Pages: 1140-1147
  • DOI: DOI:10.1038/ni.1649
  • Peer Reviewed
• [Presentation] 免疫プロテアソーム機能異常による炎症応答の分子基盤 (2012)
  • Author(s): 安友康二
  • Organizer: 日本生化学学会シンポジウム
  • Place of Presentation: 福岡県
  • Year and Date: 2012-12-14
• [Presentation] Notch provides metabolic signals in memory CD4+ T cells (2012)
  • Author(s): Koji Yasutomo
  • Organizer: 日本免疫学会シンポジウム
  • Place of Presentation: 神戸国際会議場、兵庫県
  • Year and Date: 2012-12-02
• [Remarks]
  • URL: http://immunology.hosp.med.tokushima-u.ac.jp/immunology/system/top/index.php