The roles of TLR2 and TLR4 in mouse imiquimod-induced psoriasis model

• Project/Area Number: 25461684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nihon University
• Principal Investigator: FUJITA Hideki 日本大学, 医学部, 准教授 (10323544)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: TLR / 乾癬 / マウスモデル

Outline of Final Research Achievements

Imiquimod-induced psoriasis-like dermatitis was exacerbated in TLR2-deficient (TLR2(-/-)) mice compared to wild type (WT) mice, while it was comparable between TLR4-deficient and WT groups. In the lesional skin on day 2, the expression levels of Th1 cytokines were higher in TLR2(-/-) mice than those in WT mice. On the other hand, the expression of Th17 cytokines and Foxp3 was decreased in TLR2(-/-) mice compared to WT mice. In the skin draining lymph node, the expression of TGF-beta and the number of CD4(+)Foxp3(+) cells was decreased in TLR2(-/-) mice relative to WT mice on the day 2 of imiquimod application. Taken together, elevated Th1 cytokines and suppression of regulatory T cells may account for the exacerbation of imiquimod-induced psoriasis dermatitis observed in TLR2(-/-).