Examining the epidermal resident memory T cell of psoriasis model mouse

• Project/Area Number: 20K08696
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Teikyo University
• Principal Investigator: Tada Yayoi 帝京大学, 医学部, 主任教授 (00334409)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 乾癬

Outline of Research at the Start

マウスイミキモドモデルを用いて、乾癬の寛解皮膚におけるTRMを含む皮膚免疫細胞の免疫組織学的評価を行う。TRMのIL-17、IL-22、 IFN-γなどの産生をフローサイトメトリーで測定する。IL-17産生誘導など、IL-23のソースの検索については、ランゲルハンス細胞、ケラチノサイト、樹状細胞を候補細胞として、フローサイトメトリーや免疫染色で検索する。最後に光線療法などの様々な治療法がTRMに与える影響について免疫染色、フローサイトメトリーなどを用いて検討する。

Outline of Final Research Achievements

Recently, it has been reported that resident memory T cells (TRMs), which are characteristic of psoriasis, remain in the epidermis of lesions with the ability to produce IL-17A even in remission after treatment, and may be involved in the relapse of skin rash. In this study, we confirmed the presence of TRM (CD8+CD69+CD103+) with the same characteristics in the epidermis of psoriasis IMQ model mice. We confirmed that this TRM could be activated by epidermal cells. These cells were able to produce cytokines when stimulated. The results of this study suggest that TRMs may be involved in psoriasis exacerbation by stimulating T cells to produce cytokines.

Academic Significance and Societal Importance of the Research Achievements

乾癬は慢性の炎症性皮膚疾患であるが、同じ場所に皮疹が再燃を繰り返すことが分かっており、何らかの皮疹の記憶が皮膚に残っているとされている。乾癬の表皮内に　resident memory T cell (TRM)があることがわかり、これが乾癬を治療後も表皮内に残る。我々はこのヒトのTRMと同じ性質をもつ細胞をマウスのイミキモド乾癬モデルマウス皮膚にもあることを同定した。この細胞は表皮細胞との共培養ややT細胞を活性化する刺激によりサイトカイン産生をすることから、乾癬の病態に関連すると考える。

Research Products

• [Journal Article] Serum levels of angiogenesis-related factors in patients with psoriasis. (2023)
  • Author(s): Watanabe A, Kamata M, Shimizu T, Uchida H, Sakurai E, Suzuki S, Nakajima H, Niimura Y, Ito M, Egawa S, Nagata M, Fukaya S, Hayashi K, Tanaka T, Ishikawa T, Tada Y
  • Journal Title: J Dermatol. Volume: 50 Issue: 2 Pages: 222-228
  • DOI: 10.1111/1346-8138.16588
  • Peer Reviewed
• [Journal Article] Dendritic Cells and Macrophages in the Pathogenesis of Psoriasis (2022)
  • Author(s): Kamata M, Tada Y.
  • Journal Title: Front Immunol Volume: 13 Pages: 1-10
  • DOI: 10.3389/fimmu.2022.941071
  • Peer Reviewed / Open Access
• [Journal Article] Apremilast downregulates interleukin-17 production and induces splenic regulatory B cells and regulatory T cells in imiquimod-induced psoriasiform dermatitis (2021)
  • Author(s): Uchida Hideaki、Kamata Masahiro、Shimizu Teruo、Egawa Shota、Ito Makoto、Takeshima Ryosuke、Mizukawa Itsumi、Watanabe Ayu、Tada Yayoi
  • Journal Title: Journal of Dermatological Science Volume: 104 Issue: 1 Pages: 55-62
  • DOI: 10.1016/j.jdermsci.2021.08.001
  • Peer Reviewed
• [Journal Article] Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes (2021)
  • Author(s): Okura Iori、Kamata Masahiro、Asano Yoshihide、Mitsui Aya、Shimizu Teruo、Sato Shinichi、Tada Yayoi
  • Journal Title: Journal of Dermatological Science Volume: 102 Issue: 2 Pages: 116-125
  • DOI: 10.1016/j.jdermsci.2021.04.004
  • Peer Reviewed