Abstract
Background: This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF). Methods: This study included SSc-ILD and SSc-nonILD patients who were admitted to Beijing Chaoyang Hospital between April 4th, 2013, to June 30th, 2023. Publicly available datasets, including peripheral blood monocular cell (pbmc) single-cell data, SSc, SSc-ILD pbmc transcriptome data, and SSc-ILD, IPF lung tissue transcriptome data were analyzed. Statistical analyses were conducted using the SPSS and R software, employing standard statistical methods and bioinformatics packages such as Seurat, DESeq2, enrichR, and CellChat. Results: The results revealed that the CD4+/CD8+ T cell ratio of pbmc in SSc-ILD patients was significantly higher than in SSc-nonILD patients. In IPF patients, an elevated CD4+/CD8+ T cell ratio was also observed in progressive group, and Treg and mature CD4+ T cells might cause this change. JAK-STAT pathway and the cytokine-cytokine receptor interaction pathway were activated in peripheral blood T cells of IPF patients. The CD30, CD40, and FLT3 signaling pathways were found to play crucial roles in T cell interactions with other immune cells among IPF patients. SPA17 as a commonly upregulated gene among SSc, SSc-ILD, and IPF pbmc and lung, with its expression correlating positively with disease severity and lung function progression. Conclusion: CD4+/CD8+ T cell ratio might associate with ILD initiation and progression; Treg cells and mature CD4+ T cells play key roles of it. SPA17 might serve as a pan-ILD marker and associated with lung function progression.