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PD-1 表达定义了银屑病中优先产生 IL-17A 并使用偏倚 TCR 库的表皮 CD8+CD103+T 细胞。

PD-1 Expression Defines Epidermal CD8CD103 T Cells Preferentially Producing IL-17A and Using Skewed TCR Repertoire in Psoriasis.

机构信息

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan; Allergic Disease Research Center, Chutoen General Medical Center, Kakegawa, Japan.

出版信息

J Invest Dermatol. 2021 Oct;141(10):2426-2435.e5. doi: 10.1016/j.jid.2021.03.011. Epub 2021 Apr 9.

Abstract

In psoriasis, CD8CD103 memory T cells residing in the epidermis represent an effector population capable of maintaining the condition and driving a recurrence of the disease. Tissue-infiltrating CD8 T cells expressing PD-1 are regarded as antigen-primed effector cells in others chronic inflammatory diseases. However, the expression and significance of PD-1 on skin-infiltrating CD8 T cells in human psoriasis is not known. By analyzing skin-infiltrating T cells from human psoriasis, we found that active psoriatic epidermis contained PD-1 expressing CD8CD103 T cells that correlated with the disease severity and histopathology. PD-1CD8CD103 T cells possessed a canonical psoriasis-specific resident memory phenotype with IL-23R expression and produced IL-17A, whereas PD-1CD8CD103 T cells preferentially produced IFN-γ. The diversity of skin-infiltrating T cells was dominated by CD4 T cells, while CD8 T cells, especially CD8CD103T cells, represented an oligoclonal population in active psoriasis. In addition, PD-1CD8CD103T cells used different TCR Vβs from PD-1CD8CD103T cells counterpart. In the early resolved lesion, the composition and functional status of PD-1CD8CD103T cells were markedly altered, while PD-1CD8CD103 T cells population was minimally changed. Collectively, PD-1 expression delineates a putative pathogenic subset of epidermal CD8CD103 T cells, which possibly play a role in psoriasis pathogenesis.

摘要

在银屑病中,驻留在表皮中的 CD8CD103 记忆 T 细胞代表了一种效应群体,能够维持病情并导致疾病复发。在其他慢性炎症性疾病中,组织浸润的表达 PD-1 的 CD8 T 细胞被认为是抗原激活的效应细胞。然而,在人类银屑病中,皮肤浸润的 CD8 T 细胞上 PD-1 的表达及其意义尚不清楚。通过分析人类银屑病中的皮肤浸润 T 细胞,我们发现活跃的银屑病表皮中含有与疾病严重程度和组织病理学相关的表达 PD-1 的 CD8CD103 T 细胞。PD-1CD8CD103 T 细胞具有经典的银屑病特异性驻留记忆表型,表达 IL-23R,并产生 IL-17A,而 PD-1CD8CD103 T 细胞则优先产生 IFN-γ。皮肤浸润 T 细胞的多样性主要由 CD4 T 细胞主导,而 CD8 T 细胞,特别是 CD8CD103T 细胞,在活跃的银屑病中代表一个寡克隆群体。此外,PD-1CD8CD103T 细胞使用与 PD-1CD8CD103T 细胞不同的 TCR Vβ。在早期消退的病变中,PD-1CD8CD103T 细胞的组成和功能状态发生了明显改变,而 PD-1CD8CD103 T 细胞群体的变化很小。总之,PD-1 的表达描绘了表皮 CD8CD103 T 细胞中一个潜在的致病性亚群,可能在银屑病发病机制中发挥作用。

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