Functional analysis of Clec10a in atopic dermatitis

• Project/Area Number: 17K17625
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: Kanemaru Kazumasa 筑波大学, 医学医療系, 助教 (20792500)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: アトピー性皮膚炎 / ハウスダストマイト / C型レクチン受容体 / 皮膚炎 / Clec10a / マクロファージ

Outline of Final Research Achievements

House dust mite (HDM) allergens trigger allergic diseases, including atopic dermatitis and allergic asthma. Although a C-type lectin receptor Clec10a is expressed on macrophages and dendritic cells, its function in immune responses by these myeloid cells remains incompletely understood. Here we examined whether Clec10a is involved in house dust mite (HDM)-induced allergic dermatitis.
Wild-type (WT) and Clec10a KO mice on the C57BL/6J mice background were topically applied with HDM on the skin. Clec10a KO mice showed dysregulated HDM-induced immune responses. Clec10a regulated HDM-induced inflammatory cytokines secretions from bone marrow-derived cultured MPs. In addition, Clec10a associates with signaling molecules after HDM stimulation. These results suggest that Clec10a is a receptor, which regulates HDM-induced immune response.

Academic Significance and Societal Importance of the Research Achievements

Clec10aはパターン認識受容体の1つであるC型レクチン受容体であり、主にマクロファージや樹状細胞の膜上に発現し、マウス炎症性腸疾患モデルにおいては病態に対し抑制的に機能することが報告されている (Am J Pathol, 174:144, 2009)。しかしながらアレルギーにおけるClec10aの機能は未だに報告が無い。アトピー性皮膚炎の主要アレルゲンであるハウスダストマイトに対するClec10aの機能を詳細に解明することで、アトピー性皮膚炎の病態メカニズムの解明、及び治療標的分子としての検討に繋がる。

Research Products

• [Presentation] Clec10a (MGL1/CD301a) はハウスダストマイト誘導性皮膚炎を抑制する (2018)
  • Author(s): 金丸和正、野口恵美子、伝田香里、入村達郎、田原聡子、渋谷彰
  • Organizer: 糖鎖免疫 Glyco-Immunology 2018
  • Invited
• [Presentation] Clec10a suppresses house dust mite-induced dermatitis (2017)
  • Author(s): Kazumasa Kanemaru, Emiko Noguchi, Kaori Denda-Nagai, Tatsuro Irimura, Satoko Tahara-Hanaoka, Akira Shibuya
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] Clec10a suppresses house dust mite-induced dermatitis (2017)
  • Author(s): Kazumasa Kanemaru, Kaori Denda-Nagai, Tatsuro Irimura, Satoko Tahara-Hanaoka, Akira Shibuya
  • Organizer: 第46回 日本免疫学会学術集会
• [Patent(Industrial Property Rights)] アレルギー疾患を処置することに用いるための組成物 (2019)
  • Inventor(s): 渋谷彰、金丸和正
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019