Cholinergic modulation engages a CHRM1-IL-17 neuroimmune axis to promote diabetic wound repair

Topical metrifonate, an acetylcholinesterase inhibitor, accelerates diabetic wound healing in mice by engaging a CHRM1–IL-17 neuroimmune axis.

• Why it matters: Diabetic wounds often stay stuck in persistent inflammation, failing to shift into effective repair; the mechanisms that can promote productive inflammation are unclear.
• What they did: Using a healing-associated fibroblast signature from single-cell profiling of human diabetic foot ulcers, the study tested metrifonate topically, then mapped receptor and immune pathways via receptor pharmacology, transcriptomics, and spatial transcriptomics.
• The result: CHRM1 is the principal receptor, with early IL-17-associated programs and CHRM1NK1.1 innate lymphocyte enrichment; NK1.1 depletion or IL-17A neutralization abolishes the pro-healing effect, and localized treatment also promotes repair in diabetic porcine wounds and human skin models.

AI summary of the abstract · may contain errors · not medical advice · read the paper.