Blue-Light Photobiomodulation Shapes Mast Cell and Neuronal Immunophenotypes in Murine Skin Wounds

Background/Objectives: Blue-light photobiomodulation (PBM) modulates inflammation and tissue repair, but its effects on cutaneous neuroimmune interactions remain unclear. We assessed marker co-expression in mast cells (MCs) and NSE-positive profiles, together with their spatial relationship, during acute wound healing. Methods: Fifteen male CD1 mice each received two dorsal wounds: one was treated once with blue light (410–430 nm, 20.6 J/cm2) (TW), while the other was shielded from irradiation and served as the untreated wound (UTW). Unwounded control skin (CTRL) was obtained from five separate mice. Immunofluorescence was used to assess marker co-expression in avidin-positive MCs and NSE-positive profiles at 24, 48 and 144 h. Measurements from two microscopic fields were averaged for each animal and tissue condition (n = 5 mice per time point, with paired TW and UTW samples; n = 5 separate CTRL mice). TW–UTW data were analysed by two-way repeated-measures ANOVA with Sidak’s test; CTRL comparisons were analysed by two-tailed, unpaired Mann–Whitney U tests. Results: At all time points, TWs showed significantly higher MC marker positivity for CGRP, NKA, NPY, NSE, PGP9.5 and SP than UTWs; VIP was lower at 24 h, and NGF higher at 144 h. The percentages of NSE-positive profiles co-expressing each of the eight markers were significantly higher in TWs than in UTWs at 24 h; no TW–UTW differences were detected at 48 or 144 h. Compared with CTRL, six MC markers were higher in TWs at 24 and 48 h and five at 144 h; all eight neuronal markers were higher in TWs at 24 h, with later CTRL differences being marker-specific. MC–neuronal distances were numerically shorter in TWs at all time points, but the difference was significant only at 24 h. Conclusions: Blue-light PBM was associated with differences in MC marker co-expression at all assessed time points, whereas differences in NSE-positive profiles were detected only at 24 h. These findings support PBM-associated remodelling of the cutaneous neuroimmune profile.