Transcriptomic skin niches in systemic sclerosis underpin a role for mitochondrial dysfunction.

Wang, Junqin; Hennessey, Dylan; Iyer, Aishwarya; O'Keefe, Sandra; Khan, Lamia; Redmond, Desiree; Osman, Mohammed; Gniadecki, Robert · Br J Dermatol · 2025

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Abstract

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by fibrosis, vasculopathy and immune dysregulation. Using spatial transcriptomics on the dermis of 11 patients with SSc, we identified distinct transcriptomic niches associated with fibrosis, immune activation and mitochondrial dysfunction. Our findings highlight mitochondrial dysfunction as a central mechanism in SSc pathogenesis, ranging from adaptive remodelling in immune zones to metabolic collapse in fibrotic zones, underscoring mitochondria as a therapeutic target.