The role of skin lipid in the pathogenesis of psoriasis

• Project/Area Number: 18K16047
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Inoue Sae 筑波大学, 附属病院, 病院助教 (60816528)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 乾癬 / 皮膚T細胞 / 皮膚脂肪酸 / 皮膚resident memory T細胞 / 脂質

Outline of Final Research Achievements

The involvement of skin resident memory T cells in the pathogenesis of psoriasis was investigated from the aspect of fatty acid metabolism. Resident memory T cells from psoriatic skin upregulated the expression of FABP5 compared to those from healthy control skin. The difference of FABP4 expression was not obvious. RNA-seq analysis suggested the augmented expression of enzymes related to lipid metabolism in psoriatic skin resident memory T cells compared to those from healthy controls. We were not able to define the specific fatty acids which could downregulate the expression of FABP5 and it is suggested that generally augmented uptake of fatty acid correlated to the upregulation of FABP5 in psoriatic T cells.

Academic Significance and Societal Importance of the Research Achievements

乾癬は30代と比較的低年齢での発症が多い慢性疾患であり、皮膚症状、関節症状などにより社会的生活が著しく脅かされる場合が多く、また、近年開発が進む生物学的製剤が有効である一方で治療継続が必須であるため医療費負担のインパクトも極めて大きい。本研究では、乾癬皮膚resident memory T細胞の脂肪酸取り込みが亢進していることが判明し、また、脂肪酸代謝関連酵素の発現上昇も示唆された。このことから、脂肪酸取り込みを抑制するような酵素阻害剤の外用で乾癬皮膚resident memory T細胞の機能異常を是正できる可能性が示唆され、簡易な外用による新規治療の開発に近づいたといえる。