Cross-disease immune cells atlas reveals the similarities and differences of cell characteristics and interactions in rheumatic diseases.

INTRODUCTION

Rheumatic diseases are a group of immune-mediated inflammatory disorders, in which abnormal activation of immune cells is closely related to the occurrence and development of the diseases. Previous studies have mostly been limited to single diseases or single cell types, lacking systematic comparisons of immune profiles across multiple diseases and interactions between cell types, which has restricted our understanding of the overall pattern of immune dysregulation in rheumatic diseases.

METHODS

To provide a systematic characterization of the similarities and differences in immune cells among various rheumatic diseases, this study integrated single-cell transcriptome data from peripheral blood mononuclear cells of five rheumatic diseases and healthy controls.

RESULTS

Different rheumatic diseases share some immune dysregulation modules, such as impaired function of γδ T cells. We found that the functions of γδ T cells, including immune regulation and cell proliferation, were significantly decreased in five rheumatic diseases. The analysis of cell communication suggested that the MIF and GALECTIN signaling pathways play a key role in the interaction between T cells and myeloid cells in five rheumatic diseases. However, rheumatic diseases retain their specific disease characteristics, such as different myeloid activation states. Among them, the myeloid cells in Behçet's disease patients were generally found characterized by enhanced cytotoxicity, while they showed active inflammatory states in systemic lupus erythematosus.

DISCUSSION: This study systematically characterized the immune cell characteristics and interaction networks across rheumatic diseases, revealing shared and specific immune dysregulation patterns, and provided new insights into understanding the immune mechanisms of rheumatic diseases and developing targeted therapeutic strategies.