Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis

Abstract Dysfunction of immunoinhibitory signals and persistent T cell activation reportedly play important roles in the development of vasculitis. The skin is one of the most accessible organs, and it is suitable for the characterization of immune cell signatures. However, the inhibitory checkpoint...

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Main Authors: Chie Miyabe, Yupeng Dong, Takaharu Ikeda, Kazuo Takahashi, Yoshishige Miyabe, Tamihiro Kawakami
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-99558-5
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author Chie Miyabe
Yupeng Dong
Takaharu Ikeda
Kazuo Takahashi
Yoshishige Miyabe
Tamihiro Kawakami
author_facet Chie Miyabe
Yupeng Dong
Takaharu Ikeda
Kazuo Takahashi
Yoshishige Miyabe
Tamihiro Kawakami
author_sort Chie Miyabe
collection DOAJ
description Abstract Dysfunction of immunoinhibitory signals and persistent T cell activation reportedly play important roles in the development of vasculitis. The skin is one of the most accessible organs, and it is suitable for the characterization of immune cell signatures. However, the inhibitory checkpoint molecules in the skin and their relevance to vasculitis have not been studied. Here, 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 of patients with systemic and cutaneous vasculitis. In addition, programmed death-ligand 1 (PD-L1) expression was elevated in the skin of patients with cutaneous vasculitis. Histologically, PD-L1 was highly expressed in the vessels in the skin along with CD4+ and CD8+ T-cell infiltration in patients with cutaneous vasculitis. Notably, plasma soluble PD-L1 levels were increased, and these correlated with C-reactive protein in patients with systemic vasculitis. Our findings suggest that inhibitory checkpoint molecules might be differentially modulated in the skin and peripheral blood of patients with vasculitis, and that the alteration of the PD-L1/PD-1 axis may be associated with the regulation of T-cell activation in vasculitis.
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spelling doaj.art-d62971d8fd3544cbac7a12184d4cb7022022-12-21T23:37:12ZengNature PortfolioScientific Reports2045-23222021-10-0111111110.1038/s41598-021-99558-5Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitisChie Miyabe0Yupeng Dong1Takaharu Ikeda2Kazuo Takahashi3Yoshishige Miyabe4Tamihiro Kawakami5Division of Dermatology, Tohoku Medical and Pharmaceutical UniversityDivision of Dermatology, Tohoku Medical and Pharmaceutical UniversityDivision of Dermatology, Tohoku Medical and Pharmaceutical UniversityDivision of Dermatology, Tohoku Medical and Pharmaceutical UniversityDepartment of Cell Biology, Institute for Advanced Medical Sciences, Graduate School of Medicine, Nippon Medical SchoolDivision of Dermatology, Tohoku Medical and Pharmaceutical UniversityAbstract Dysfunction of immunoinhibitory signals and persistent T cell activation reportedly play important roles in the development of vasculitis. The skin is one of the most accessible organs, and it is suitable for the characterization of immune cell signatures. However, the inhibitory checkpoint molecules in the skin and their relevance to vasculitis have not been studied. Here, 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 of patients with systemic and cutaneous vasculitis. In addition, programmed death-ligand 1 (PD-L1) expression was elevated in the skin of patients with cutaneous vasculitis. Histologically, PD-L1 was highly expressed in the vessels in the skin along with CD4+ and CD8+ T-cell infiltration in patients with cutaneous vasculitis. Notably, plasma soluble PD-L1 levels were increased, and these correlated with C-reactive protein in patients with systemic vasculitis. Our findings suggest that inhibitory checkpoint molecules might be differentially modulated in the skin and peripheral blood of patients with vasculitis, and that the alteration of the PD-L1/PD-1 axis may be associated with the regulation of T-cell activation in vasculitis.https://doi.org/10.1038/s41598-021-99558-5
spellingShingle Chie Miyabe
Yupeng Dong
Takaharu Ikeda
Kazuo Takahashi
Yoshishige Miyabe
Tamihiro Kawakami
Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
Scientific Reports
title Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
title_full Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
title_fullStr Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
title_full_unstemmed Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
title_short Immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
title_sort immune checkpoint molecule expression is altered in the skin and peripheral blood in vasculitis
url https://doi.org/10.1038/s41598-021-99558-5
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