Exacerbation mechanism of allergic skin inflammation

• Project/Area Number: 17K08803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: KITAJIMA MASAYUKI 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (00401000)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アレルギー性皮膚炎 / TSLP / Th2 / IL-4 / CD4 / 炎症増悪化

Outline of Final Research Achievements

Thymic Stromal LymphoPoietin (TSLP) is an important mediator for the development of Th2-type allergic diseases, including atopic dermatitis (AD), in both human patients and murine models. However, the physiological role of TSLPR signaling by CD4 T cells in the development of skin inflammation by chronic allergen exposure remains to be elucidated. To investigate the role of TSLP in the progression of allergic inflammation, we used Tslpr conditional KO mice and a newly developed skin chronic inflammation model that features repetitive allergen challenge. In this study, we demonstrated that TSLPR on CD4 T cells is critical for development of chronic skin inflammation through enhancing IL-4 production and inhibiting cell death.

Academic Significance and Societal Importance of the Research Achievements

申請者は新規慢性皮膚炎症マウスモデルを構築し、アレルギー性皮膚炎の重症化メカニズムの一端を明らかにした。このメカニズムは、早期炎症応答による炎症環境の変化がさらなる炎症重症化を導くという新しい概念を提示する意義深い成果である。本研究成果は、皮膚慢性炎症根治治療のための研究基盤となる炎症増悪化メカニズムのさらなる解明に繋がることが期待できる社会的意義の大きい成果でもある。

Research Products

• [Int'l Joint Research] Benaroya Research Institute(米国)
• [Journal Article] Critical Role of TSLP Receptor on CD4 T Cells for Exacerbation of Skin Inflammation (2020)
  • Author(s): Kitajima Masayuki、Kubo Masato、Ziegler Steven F.、Suzuki Harumi
  • Journal Title: The Journal of Immunology Volume: - Issue: 1 Pages: 27-35
  • DOI: 10.4049/jimmunol.1900758
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The role of Nqo1 in contact hyper-sensitivity (2019)
  • Author(s): Kitajima Masayuki, Suzuki Harumi
  • Journal Title: Clinical immunology & allergology Volume: 72 Pages: 1-6
  • NAID: 40021959344
• [Journal Article] NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IκB-ζ degradation. (2018)
  • Author(s): 1. Kimura, A., Kitajima, M., Nishida, K., Serada, S., Fujimoto, M., Naka, T., Fuji-Kuriyama, Y., Ito, T., Handa, H., Tanaka, T, Yoshimura, A., Suzuki, H.
  • Journal Title: Journal of experimental medicine Volume: 215 Issue: 8 Pages: 2197-2200
  • DOI: 10.1084/jem.20172024
  • Peer Reviewed / Open Access
• [Journal Article] Cutting Edge: Nqo1 Regulates Irritant Contact Hypersensitivity against Croton Oil through Maintenance of Dendritic Epidermal T Cells (2018)
  • Author(s): Kitajima Masayuki、Kimura Akihiro、Suzuki Harumi
  • Journal Title: The Journal of Immunology Volume: 200 Issue: 5 Pages: 1555-1559
  • DOI: 10.4049/jimmunol.1701389
  • Peer Reviewed
• [Journal Article] Rasal3-mediated T cell survival is essential for inflammatory responses (2018)
  • Author(s): Muro Ryunosuke、Nitta Takeshi、Kitajima Masayuki、Okada Toshiyuki、Suzuki Harumi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 496 Issue: 1 Pages: 25-30
  • DOI: 10.1016/j.bbrc.2017.12.159
  • Peer Reviewed / Open Access
• [Journal Article] Baculovirus directly activates murine NK cells via TLR9 (2017)
  • Author(s): Moriyama, T., Suzuki, T., Chang, Mo., Kitajima, M., Takaku, H.
  • Journal Title: The Journal of Cancer Gene and Cellular Therapies Volume: - Issue: 4 Pages: 175-179
  • DOI: 10.1038/cgt.2017.2
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Critical role of TSLP receptor on CD4 T cells for exacerbation of Th2-type skin inflammaion. (2019)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: The 48th Annual meeting of the Japanese society for Immunology
• [Presentation] Significant role of TSLP receptor on CD4 T cells in chronic skin inflammation. (2019)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: The 17th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] Critical role of TSLPR on CD4 T cells for exacerbation of type 2 skin inflammation. (2019)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: The 29th Kyoto T Cell Conference
• [Presentation] Critical role of TSLP receptor on CD4 T cells for exacerbation of skin inflammation. (2019)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: ThymE: T cell and thymus biology
  • Int'l Joint Research
• [Presentation] The Pathogenesis of TSLP-responded Th2 cells in exacerbation of skin inflammation. (2018)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: The 47th Annual meeting of the Japanese society for Immunology, Fukuoka, Japan
• [Presentation] Role of TSLPR on CD4 T cells in exacerbation of skin inflammation. (2017)
  • Author(s): M Kitajima, SF Ziegler, H Suzuki
  • Organizer: The 46th Annual meeting of the Japanese society for Immunology
• [Presentation] The novel ubiquitin ligase complex, NQO1-PDLIM2 inhibits TLR-dependent production of selective cytokines by degrading IκB-ζ. (2017)
  • Author(s): A Kimura, M Kitajima, H Suzuki
  • Organizer: The 46th Annual meeting of the Japanese society for Immunology
• [Presentation] The novel ubiquitin ligase complex, NQO1-PDLIM2 inhibits TLR-dependent production of selective cytokines by degrading. (2017)
  • Author(s): A Kimura, M Kitajima, H Suzuki
  • Organizer: The Cytokines
  • Int'l Joint Research