BACKGROUND: Plasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to explore the metabolic profile of pDCs in SSc and their potential contribution to the disease. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors and SSc patients. SCENITH™, a single-cell flow cytometry-based method, was applied to infer the metabolic profile of circulating pDCs from patients with SSc. pDCs (CD304 RESULTS: Circulating pDCs from ten healthy donors and fourteen SSc patients were analysed. pDCs from anti-centromere antibody-positive (ACA CONCLUSIONS: An innovative single cell flow cytometry-based methodology was applied to analyse the metabolic profile of pDCs from SSc patients. Our results suggest that pDCs from ACA