Single-cell sequencing of PBMC characterizes the transformation of T cell subsets in the inflammatory microenvironment of RA-ILD

Abstract

Abstract Rheumatoid arthritis-interstitial lung disease (RA-ILD), associated with Rheumatoid Arthritis (RA), typically manifests as usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). However, the pathogenic mechanisms underlying RA and its related ILD are not fully understood. The progression of single-cell sequencing technology has enhanced our comprehension of the inflammatory environment, offering potential insights into inflammation-related cells. In this study, we conducted single-cell sequencing and cell communication analysis on peripheral blood mononuclear cells (PBMCs) from patients with RA, RA + UIP, and RA + NSIP. Our results revealed that blood cells from patients were annotated as T cells, NK cells, neutrophils, red blood cells, B cells, monocytes, macrophages, dendritic cells, platelets, and hematopoietic stem cells, indicating the accumulation of T cells in the inflammatory environment. Temporal analysis suggested a differentiation trend in T cells: CD4 + T cells, regulatory T cells, CD69 + T cells, and CD8 + T cells. Subgroup enrichment analysis of T cells identified significantly differentially expressed genes (DEGs) enriched in pathways such as rheumatoid arthritis, IL-17 signaling, Th1 and Th2 cell differentiation, Th17 cell differentiation, and TNF signaling. Further investigation revealed the pro-inflammatory characteristics of this subgroup, and cell communication results indicated a pivotal role of T cells. In summary, our comprehensive analysis identified T cells as crucial mediators in RA-ILD and unveiled potential pathways, including interactions among HLA, MIF, CLEC2C ligands, and CD8A, CD8B, CD74 receptors. These findings provided potential biomarkers for effective treatment targets and intervention strategies, deepening our understanding of T cell participation in the immune pathogenesis of RA-ILD.