Fibroblast-directed melanocyte recruitment via Cxcl12-Cxcr4 cascade promotes post-inflammatory hyperpigmentation and skin barrier protection in zebrafish

Post-inflammatory hyperpigmentation (PIH), a prevalent dermatological condition, is classically attributed to melanocyte overactivation in situ. However, the precise triggers and physiological significance of melanocyte responses remain elusive. Using an acetic acid corrosion-induced zebrafish PIH model, here we demonstrate that melanocyte migration to the inflammatory site is a key pathogenic driver of hyperpigmentation. This migration is largely orchestrated by fibroblasts, but not macrophages or neutrophils, which secrete the chemokine cxcl12a upon injury, recruiting melanocytes via the cxcl12a-cxcr4a signaling axis. Beyond hyperpigmentation, we reveal that melanocytes function as a dual protective barrier against both UV-induced DNA damage and microbial invasion in response to acetic acid corrosion-induced injury. Our findings provide new insights into PIH pathogenesis and uncover the non-canonical barrier functions of melanocytes in skin inflammation and repair. Overall design: In this experiment, we have conducted acetic acid corrosion in four trunk sites in 2 dpf embryos,cut the trunk region at 3 dpf, dissociated the embryos into single cell suspension and performed FACS sorting of dsRed positive fibroblasts. In each biological replicate, around 30 embryos were harvested and 500 fibroblsts were sorted into lysis buffer. Smartseq2 protocol was utilized for double strand cDNA library construction.