Analysis of the pathogenic mechanisms of autoimmune diseases induced by overproduction of cytokine TSLP

• Project/Area Number: 21790488
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: ISEKI Masanori 独立行政法人国立国際医療研究センター, 免疫制御研究部, 免疫応答修飾研究室長 (30532353)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アレルギー・免疫関連疾患 / 自己免疫疾患 / サイトカイン / マウスモデル / 免疫学 / アレルギー・ぜんそく

Research Abstract

It has been known that the cytokine thymic stromal lymphopoietin(TSLP) promotes the differentiation of type 2 helper T cells(Th2 cells) and induces allergic inflammations including asthma and atopic dermatitis. However, the details of its pathogenic mechanisms were still remained unclear. In this research, we found that TSLP directly stimulates CD4^+T cells and induces Th2 condition in vivo, which leads to polyclonal B cell activation and the autoimmune disease. These results would be applied to the development of novel therapies for immune diseases.

Research Products

• [Journal Article] Thymic stromal lymphopoietin(TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4^+T cells and IL-4 (2012)
  • Author(s): Iseki M, Omori-Miyake M, Xu W, Sun X, Takaki S, Rawlings DJ, Ziegler SF
  • Journal Title: International Immunology Volume: Vol.24 Issue: 3 Pages: 183-195
  • DOI: 10.1093/intimm/dxr113
  • Peer Reviewed
• [Journal Article] Dibutyl Phthalate-Induced Thymic Stromal Lymphopoietin Is Required for Th2 Contact Hypersensitivity Responses (2010)
  • Author(s): Larson RP, Zimmerli SC, Comeau MR, Itano A, Omori M, Iseki M, Hauser C, Ziegler SF
  • Journal Title: The Journal of Immunology Volume: Vol.184 Issue: 6 Pages: 2974-2984
  • DOI: 10.4049/jimmunol.0803478
  • Peer Reviewed
• [Journal Article] Dibutyl Phthalate-Induced Thymic Stromal Lymphopoietin Is Required for Th2 Contact Hypersensitivity Responses (2010)
  • Author(s): Ryan P.Larson, et al.
  • Journal Title: The Journal of Immunology Volume: 184 Pages: 2974-2984
  • Peer Reviewed
• [Journal Article] Dibutyl Phthalate-Induced Thymic Stromal Lymphopoietin Is Required for Th2 Contact Hypersensitivity Responses (2010)
  • Author(s): Ryan P.Larson, et al.
  • Journal Title: The Journal of Immunology 184 Pages: 2974-2984
  • Peer Reviewed
• [Presentation] An autoimmune disease-associated gene, Lnk/Sh2b3 controls signaling of inflammatory cytokines in dendritic cells and regulates regulatory T and helper T cell development (2011)
  • Author(s): 森泰三、井関将典、高木智, 他
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] Expression and function of MafB, a target transcription factor of Btk-mediated signaling in B cells and its relation to autoimmunity (2011)
  • Author(s): 福田誠、井関将典、高木智, 他
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] セリアック病及び1型糖尿病関連遺伝子Lnk/Sh2b3欠損はCD8+T細胞による腸管絨毛の炎症性萎縮をおこす (2011)
  • Author(s): 安楽正輝、井関将典、高木智, 他
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] IgE-specific impairment in humoral immune responses by the absence of Aps/Sh2b2, a member of Lnk/Sh2b adaptor family (2011)
  • Author(s): Iseki M, Takaki S
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-27
• [Presentation] IgE-specific impairment in humoral immune responses by the absence of Aps/Sh2b2, a member of Lnk/Sh2b adaptor family (2011)
  • Author(s): 井関将典、高木智
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-27
• [Presentation] Thymic stromal lymphopoietin(TSLP)-induced polyclonal B cell activation and autoimmunity are mediated by CD4^+T cells and IL-4 (2010)
  • Author(s): Iseki M, Omori-Miyake M, Xu W, Sun X, Takaki S, Rawlings DJ, Ziegler SF
  • Organizer: International Congress of Immunology 2010
  • Place of Presentation: 神戸ポートピアホテル、神戸国際展示場(神戸)
  • Year and Date: 2010-08-27
• [Presentation] Thymic stromal lymphopoietin (TSLP)-induced polyclonal B cell activation and autoimmunity are mediated by CD4+ T cells and IL-4 (2010)
  • Author(s): 井関將典, 他
  • Organizer: International Congress of Immunology 2010
  • Place of Presentation: 神戸ポートピアホテル神戸国際展示場(神戸)
  • Year and Date: 2010-08-27
• [Presentation] Lnk/SH2B3, a gene associated with risk of several autoimmune diseases regulates proliferation and retinoic acid production of dendritic cells (2010)
  • Author(s): 岩崎由希子、井関將典, 他
  • Organizer: International Congress of Immunology 2010
  • Place of Presentation: 神戸ポートピアホテル神戸国際展示場(神戸)
  • Year and Date: 2010-08-25
• [Presentation] The maintenance of gut-associated lymphoid tissues regulated by Lnk/Sh2B3 adaptor, a shared risk factor gene associated with type 1 diabetes and celiac disease (2010)
  • Author(s): 片山緩子、井関將典, 他
  • Organizer: International Congress of Immunology 2010
  • Place of Presentation: 神戸ポートピアホテル神戸国際展示場(神戸)
  • Year and Date: 2010-08-25
• [Presentation] TSLP modulates TH1 and TH2 responses in the skin (2010)
  • Author(s): Ryan P.Larson、井関將典, 他
  • Organizer: International Congress of Immunology 2010
  • Place of Presentation: 神戸ポートピアホテル神戸国際展示場(神戸)
  • Year and Date: 2010-08-25
• [Presentation] Thymic stromal lymphopoietin(TSLP)-induced polyclonal B cell activation and autoimmunity are mediated by CD4^+T cells and IL-4 (2009)
  • Author(s): Iseki M, Omori-Miyake M, Shih WX, Sun X, Rawlings DJ, Ziegler SF
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02
• [Presentation] Thymic atromal lymphapoietin (TSLP)-iaduced polyclonal B cell activation and autoimmunity are mediated bY CD4+ T cells and IL-4 (2009)
  • Author(s): 井関將典, 他
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-02