This study aimed to conduct a comprehensive analysis of immune cell composition in SSc by simultaneously examining blood, skin, and subcutaneous adipose tissue.<h4>Patients and methods</h4>Using spectral flow cytometry, we profiled major immune cell subsets and explored their associations with clinical features of SSc.<h4>Results</h4>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. This evidence concerns the gene MPPE1 and systemic sclerosis.