Lymphatic dysfunction involvement in psoriasis like skin inflammation, atopic dermatitis, and skin infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19708
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: Yamada Daisuke 東京大学, 医学部附属病院, 助教 (90770826)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: リンパ浮腫 / イミキモド誘発乾癬様皮膚炎 / 自然発癌 / サイトカイン蛋白の貯留

Outline of Final Research Achievements

In mice with lymphatic dysfunction, imiquimod-induced psoriasis like inflammation was deteriorated. In addition, larger and more aggressive tumors were formed in TPA- and DMBA-induced skin tumorigenesis model in mice with lymphatic dysfunction. Inconsistent with such results, mRNA expression levels of proinflammatory and prooncogenic cytokines in lesional skin after imiquimod or DMBA administration were comparable between mice with lymphatic dysfunction and wild type mice. On the other hand, we found that protein expression levels of proinflammatory and prooncogenic cytokines in lesional skin after imiquimod or DMBA administration were increased in mice with lymphatic dysfunction. We also revealed that phosphorylation of STAT3 induced by various cytokines was upregulated in epidermal keratinocytes of mice with lymphatic dysfunction. These results suggest that lymphatic dysfunction caused cytokine protein accumulation, resulting in exacerbation of inflammation and carcinogenesis.

Free Research Field

リンパ浮腫

Academic Significance and Societal Importance of the Research Achievements

リンパ浮腫が皮膚の炎症や幾つかの腫瘍の発生母地になることは知られていたが、その機序ははっきりとしていなかった。今回、研究代表者は、リンパ浮腫が局所における起炎症性、発がん性サイトカインの蛋白貯留を引き起こし、結果として、皮膚の炎症、腫瘍の発生につながることを見出した。貯留したサイトカインの分解などの治療がリンパ浮腫における長期的な皮膚炎、腫瘍の発生を予防できる可能性があり、リンパ浮腫の新規治療として、検討することができるようになったと思われる。