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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 and , alongside an expansion of Th2 and proinflammatory, steroid-resistant Th17 cells. Furthermore, Tregs exhibited a destabilized state characterized by high and reduced 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.