Role of cholesterol sulfate in the homeostasis of the epithelial immune microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20761
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Akiyoshi Sayaka 九州大学, 生体防御医学研究所, 助教 (70966150)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 炎症 / 乾癬 / 上皮-免疫微小環境 / 免疫細胞 / コレステロール硫酸 / DOCKファミリー分子

Outline of Final Research Achievements

We hypothesized that cholesterol sulfate (CS) is involved in the severity of inflammation in a model of psoriasis-like dermatitis. As a result of functional analysis, we identified the localization of CS and its synthetic enzyme SULT2B1-expressing cells in the skin. In addition, we found important clues regarding inflammatory cytokines, chemokines, and immune cells associated with CS in the inflammatory state of the skin. CS is a metabolite that inhibits the function of DOCK2, which is specifically expressed on immune cells and acts as a cytoskeletal regulator. These findings suggest that CS suppresses skin inflammation through a mechanism involving DOCK2.

Free Research Field

免疫・炎症

Academic Significance and Societal Importance of the Research Achievements

乾癬は、外部の有害因子を排除するメカニズムに偏りが起きた際、上皮細胞と免疫細胞の相互作用による炎症ループが形成される代表的な皮膚疾患である。本研究では、上皮細胞において、C Sと免疫細胞が関与した乾癬の病態メカニズムの一端を解明し、CSが炎症ループの病態克服のための新たな標的分子となり得ることを示した。よって、本疾患における炎症の継続・悪化を抑制するような、有効な治療法開発に貢献できる可能性がある。