Multifaceted Analysis of p19 Including Cytokines Produced by Psoriatic Keratinocytes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22739
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Okayama University
• Principal Investigator: Sugihara Satoru 岡山大学, 大学病院, 助教 (20874861)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: p19 / IL-23 / IL-39 / psoriasis / EBI3

Outline of Final Research Achievements

IL-23(p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. And its antibodies are highly effective against psoriasis. IL-39 (p19/Epstein-Barr virus-induced3 (EBI3)), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. We hypothesized that IL-39, like IL-23, contributes to the pathogenesis of psoriasis.
Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

尋常性乾癬は表皮肥厚および好中球・T細胞浸潤を特徴とする慢性炎症性皮膚疾患である。病変部表皮角化細胞は過剰な細胞増殖と免疫応答を示し、病態形成に大きく関与する。同細胞はIL-23（p19とp40のヘテロダイマー）およびIL-39（p19とEBI3（EBV-induced gene 3）のヘテロダイマー）を発現すると報告されているが、IL-23・IL-39以外のp19含有サイトカインの発現に関する報告はまだない。
本研究において、これらのサブユニットが乾癬の病態で増強することが判明し、新規のサイトカインの存在の可能性も示唆された。本研究成果は新規治療の開発に繋がる可能性がある。