Bold claim: the skin’s metabolism may be fueling systemic inflammation in dermatomyositis, revealing a potential new path for therapies. A recent study used single‑cell RNA sequencing and proteomics to map the cellular makeup of DM skin lesions and connect those skin changes to broader immune activation throughout the body.
Systemic inflammation starts in the skin’s fibroblasts
By analyzing adult DM skin samples at single‑cell resolution, researchers found that fibroblasts—not immune cells—are the primary signaling hubs driving inflammation in inflamed skin. These “inflammatory fibroblasts” showed pronounced activation of the type I interferon (IFN‑I) pathway, a key sign of immune dysregulation, and were closely tied to higher levels of the chemokine CXCL10.
A new mechanism emerged: the CXCL10–glycolysis axis. Proteomic and transcriptomic data from skin and blood indicate that heightened glycolytic activity within inflammatory fibroblasts correlates with systemic inflammatory signals. This metabolic shift appears to amplify immune activation beyond the skin, linking local disease activity to the overall inflammatory burden.
In a preclinical autoimmune myositis model, blocking glycolysis with 2‑deoxy‑D‑glucose (2DG) markedly reduced inflammation, reinforcing the idea that metabolic reprogramming helps drive disease, not just accompany it. Together, these results point to metabolism, especially glycolysis, as a promising target for DM therapies.
Clinical implications and questions for future work
The findings challenge the long‑standing view that immune cells are the primary drivers of DM skin inflammation, instead highlighting a pivotal role for fibroblasts and metabolic dysfunction. The connection between skin pathology and systemic inflammation emphasizes the importance of treating the disease as a whole. The authors advocate for more research into metabolism‑targeted treatments and propose incorporating metabolomic and proteomic profiling into routine care to better classify patients and tailor therapies.
Reference
Xu X et al. scRNA‑seq and proteomics uncover glycolytic dysregulation linking skin and systemic inflammation in dermatomyositis. Br J Dermatol. 2025. doi: 10.1093/bjd/ljaf486.
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