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单细胞转录组揭示亚急性皮肤型红斑狼疮皮肤病变的免疫病理细胞组成。

Single-cell transcriptome reveals immunopathological cell composition of skin lesions in subacute cutaneous lupus erythematosus.

作者信息

Zheng Meiling, Hu Zhi, Zhou Wenhui, Kong Yi, Wu Ruifang, Zhang Bo, Long Hai, Jia Sujie, Lu Qianjin, Zhao Ming

机构信息

Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha 410011, China; Research Unit of Key Technologies of Diagnosis and Treatment for Immune-related Skin Diseases, Chinese Academy of Medical Sciences, Changsha 410011, China.

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.

出版信息

Clin Immunol. 2022 Dec;245:109172. doi: 10.1016/j.clim.2022.109172. Epub 2022 Nov 5.

Abstract

Subacute cutaneous lupus erythematosus (SCLE) is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythemas, the pathological mechanism of which is poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing (scRNA-seq) of SCLE skin lesions and integrated the scRNA-seq data from skin tissues of healthy controls (HCs). Our results identified expanded fibroblasts and keratinocytes subtypes, abnormally activated lymphocyte and inflammatory M1 macrophages in SCLE. In SCLE, stromal cells, such as keratinocytes and fibroblasts, showed enhanced chemotactic functions for recruiting immune cells. Importantly, interferon-related genes were identified as key intermediate genes in the potential trajectory of fibroblasts, keratinocytes, and B cells from HCs to SCLE. Our investigation provides a comprehensive description of cell composition in SCLE and highlights several important clues for understanding the pathogenesis of SCLE.

摘要

亚急性皮肤型红斑狼疮(SCLE)是皮肤型红斑狼疮的一种临床亚型,表现为银屑病样或环状丘疹伴鳞屑性红斑,其病理机制尚不清楚。为了研究SCLE的免疫发病机制,我们对SCLE皮肤病变进行了单细胞RNA测序(scRNA-seq),并整合了来自健康对照(HC)皮肤组织的scRNA-seq数据。我们的结果鉴定出SCLE中扩增的成纤维细胞和角质形成细胞亚型、异常活化的淋巴细胞和炎性M1巨噬细胞。在SCLE中,角质形成细胞和成纤维细胞等基质细胞表现出增强的趋化功能以募集免疫细胞。重要的是,干扰素相关基因被鉴定为从HC到SCLE的成纤维细胞、角质形成细胞和B细胞潜在轨迹中的关键中间基因。我们的研究全面描述了SCLE中的细胞组成,并突出了几个理解SCLE发病机制的重要线索。

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