Single-cell landscape of immune cells in multiple autoimmune diseases

Lin Zhu; Wujianan Sun; Kun Chen; Zitian Liu; Meifang Tang; Chen Jiang; Yu Shi; Qian Liu; Wen Zhang; Junyu Wang; Ao Zheng; Jun Lin; Guosheng Wang; Xiaomei Li; Xu Liu; Kun Qu

doi:10.1016/j.isci.2025.114515

Single-cell landscape of immune cells in multiple autoimmune diseases

iScience. 2025 Dec 20;29(1):114515. doi: 10.1016/j.isci.2025.114515. eCollection 2026 Jan 16.

Authors

Lin Zhu^{1

2}, Wujianan Sun¹, Kun Chen¹, Zitian Liu¹, Meifang Tang¹, Chen Jiang^{1

2}, Yu Shi¹, Qian Liu¹, Wen Zhang¹, Junyu Wang¹, Ao Zheng¹, Jun Lin¹, Guosheng Wang¹, Xiaomei Li¹, Xu Liu¹, Kun Qu^{1

2

3}

Affiliations

¹ Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, State Key Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230021, China.
² Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, China.
³ School of Artificial Intelligence and Data Science, University of Science and Technology of China, Hefei 230026, China.

Abstract

Autoimmune pathologies arise from dysregulated immune activation, yet conserved molecular programs across autoimmune contexts remain incompletely characterized. Here, we analyzed integrative single-cell RNA sequencing data of over 1.3 million cells from 239 samples spanning six autoimmune diseases, revealing disease-specific and cell type-specific transcriptional programs. Systematic immune profiling identified 41 functionally annotated gene clusters (GCs) with cross-disease activation. We identified a cytotoxic CD8 ⁺ T cell-enriched gene cluster (GC40) that drives enhanced cytotoxic function and clonal expansion across four autoimmune diseases. In parallel, we identified a secretory granule lumen-associated GC08 that is highly expressed in CD14 ⁺ monocytes and promotes plasma cell activation through upregulation of TNFSF13B secretion. Furthermore, we leveraged a disease classifier to discriminate autoimmune disease types and healthy states. Our study provides both a resource and a predictive framework at the single-cell level, supporting future targeted therapies for autoimmune diseases.

Keywords: Bioinformatics; Genomics; Immunology.