Transcriptional landscape of CD4+ T cells in Systemic Sclerosis

Abstract Objective This resource deeply characterizes the CD4+ T cell subpopulations populations in SSc patients, with a novel single-cell RNA sequencing (scRNA-seq) approach, offering unprecedented insights into the cellular and molecular underpinnings of the disease. Methods We performed scRNA-seq to analyze over 80,000 CD4+ T cells from 8 SSc patients and 8 healthy controls, integrating abundance, transcriptional, and TCR repertoire analysis, to define CD4+ T cell subtype-specific signatures associated with SSc. Results SSc CD4+ T cells displayed a global interferon-driven activation signature and significantly reduced TNFα signaling. Key transcriptomic alterations included the downregulation of SOX4 and CD83 , alongside an expansion of Th2 and proinflammatory, steroid-resistant Th17 cells. Furthermore, Tregs exhibited a destabilized state characterized by high FCRL3 and reduced FOXP3 expression. Finally, TCR repertoire analysis identified increased clonal expansion specifically within the central memory (Tcm) compartment. Conclusion Together, this data revealed SSc-associated cell population states in CD4+ T cells with unique transcriptomic signatures and provided a publicly accessible interactive platform to facilitate exploration of this dataset by the research community.