Immune cells composition in the skin and subcutaneous adipose tissue of patients with systemic sclerosis

Background and objectives: Systemic sclerosis (SSc) is a rare, chronic autoimmune disease characterized by fibrosis of the skin and/or internal organs. Emerging evidence suggests that subcutaneous adipose tissue may contribute to systemic inflammation and fibrosis in SSc. This study aimed to conduct a comprehensive analysis of immune cell composition in SSc by simultaneously examining blood, skin, and subcutaneous adipose tissue. Patients and Methods: Using spectral flow cytometry, we profiled major immune cell subsets and explored their associations with clinical features of SSc. Results: Patients with mild skin fibrosis (low mRSS) exhibited increased cDC1, moDC, and ThGM-CSF cells in the skin, alongside with an influx of Th22 cells and reduced terminal NK cells in subcutaneous adipose tissue. In SSc patients with lung fibrosis, peripheral blood showed decreased NK cells and increased CD8⁺ T cells. Anti-Scl-70-positive patients demonstrated elevated CD8⁺ effector T cells, whereas anti-centromere-positive patients showed increased ThGM-CSF cells in the skin. Conclusions: These findings highlight the potential role of distinct immune subsets for disease progression and tissue-specific fibrosis in SSc.