Fig. 7: Graphical scheme of this study.

CITE-seq analysis of PBMCs from patients with SSc (n = 21) or HDs (n = 6) identified distinct immune abnormalities in SSc patients with SRC or ILD. Patients with SRC demonstrated specific enrichment of CD14⁺ monocytes with increased EGR1 expression and activation of NF-κB–related pathways. Trajectory analysis indicated their differentiation into macrophages with elevated expression of THBS1 in the kidney. Clinically, changes in monocyte EGR1 expression show potential as a biomarker for monitoring the disease progression of SRC. In patients with SSc-ILD, CD8⁺ TEMs with increased type II ISG expression were enriched in PBMCs. A similar cell population was also enriched in the lung tissue of patients with advanced SSc-ILD, suggesting migration of CD8⁺ T cells from peripheral blood to the lung, mediated by chemokine receptors such as CXCR3 and CCR5. SSc systemic sclerosis, HD healthy donor, PBMC peripheral blood mononuclear cells, CITE-seq Cellular Indexing of Transcriptomes and Epitopes by Sequencing, SRC scleroderma renal crisis, ECM extracellular matrix, ILD interstitial lung disease, ISG interferon signature genes, TEMs effector memory T cells. Created in BioRender. Shimagami, H. (2025) https://BioRender.com/m7mo04j.