The role of immune checkpoint molecules in cutaneous vasculitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17813
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokyo Women's Medical University (2020-2023); Tohoku Medical and Pharmaceutical University (2019)
• Principal Investigator: Miyabe Chie 東京女子医科大学, 医学部, 非常勤講師 (80540426)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 血管炎 / 自己免疫性疾患 / T細胞

Outline of Final Research Achievements

We investigated the profile of immune checkpoint molecules in the skin and peripheral blood of patients with vasculitis and healthy donors. We found that some of the inhibitory checkpoint molecules, including programmed cell death 1 receptor (PD-1), were elevated in T-cells in the blood. In addition, programmed death-ligand 1 (PD-L1) expression was elevated in the skin of patients with vasculitis. Histologically, PD-L1 was highly expressed in the vessels in the skin along with CD4+ and CD8+ T-cell infiltration in patients with vasculitis. Notably, plasma soluble PD-L1 levels were also increased, and these correlated with fever, C-reactive protein, and creatinine titers in patients with vasculitis. Our findings suggest that inhibitory checkpoint molecules might be differentially modulated in the skin and peripheral blood, and that the alteration of the PD-L1/PD-1 axis may be associated with the regulation of T-cell activation in vasculitis.

Free Research Field

血管炎

Academic Significance and Societal Importance of the Research Achievements

本研究では、小型血管炎で症状の現れやすい皮膚組織、および末梢血を用いて、小型血管炎発症における抑制性共刺激分子の動態を明らかにした。皮膚血管炎では、T細胞活性化マーカーの発現が上昇している一方で、PD-L1/PD-1による抑制性シグナルも亢進し、皮膚と末梢血で異なる抑制性共刺激因子の構成を示す可能性が示唆された。皮膚血管炎は、全身症状の前駆的な症状を呈することもあれば、逆に自然軽快することも少なくない。この抑制性共刺激因子による免疫反応の制御が、皮膚血管炎の収束に何らかの役割を果たすことが推察され、血管炎の予後の予測に有用な情報の一つになる可能性がある。