Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus

作者：Qiaolin Wang, Yutong Wu, Lianlian Ouyang, Xiaoli Min, Meiling Zheng, Lingyu Gao, Xiaoyun Chen, Zhi Hu, Shuang Yang, Wenjuan Jiang, Sujie Jia, Qianjin Lu, Ming Zhao · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06147-5 · 被引用次数：5 · 研究领域：Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis、Immune cells in cancer

BACKGROUND: The small intestine harbors a rich array of intestinal intraepithelial lymphocytes (IELs) that interact with structural cells to collectively sustain gut immune homeostasis. Dysregulation of gut immune homeostasis was implicated in the pathogenesis of multiple autoimmune diseases, however, whether this homeostasis is disrupted in a lupus autoimmune background remains unclear. METHODS: We performed single-cell RNA sequencing (scRNA-seq) analyses to elucidate immune and structural milieu in the intestinal epithelium of MRL/Lpr lupus mice (Lpr mice) and MRL/Mpj control mice (Mpj mice). Comprehensive analyses including unsupervised clustering, trajectories, and cellular communication were performed. The primary findings from scRNA-seq were further validated by quantitative polymerase chain reaction (qPCR), flow cytometry, and in vivo experiments including selenium supplementation. RESULTS: We observed a significant reduction in CD8αα + IELs, accompanied by a marked increase in CD8αβ + IELs in Lpr mice. Additionally, subsets of CD8 + IELs exhibiting significantly enhanced effector functions were found to be markedly enriched in Lpr mice. Intercellular communication patterns within intestinal epithelial immune and structural cells were found to be specifically altered in Lpr mice. Moreover, scRNA-seq revealed significantly decreased intestinal TCRγδ T cells (γδT) associated with reduced aryl-hydrocarbon receptor repressor (AHRR) expression and subsequent oxidative stres...