Human skin mast cells express photoreceptors, and blue light inhibits their degranulation

Background: Allergic skin reactions are driven by dermal mast cells (MCs) and exhibit circadian differences. In human skin, circadian rhythms may be regulated by cryptochromes (CRYs) and opsins (OPNs), photoreceptors (PRs), which were recently identified to be expressed in a number of human cutaneous cell types. Whether human skin MCs express these receptors is currently unknown Method: We obtained MCs from human skin (breast, foreskin, eyelids) and used also cultured CD34‐positive peripheral blood stem cell‐derived MCs (PSCMCs) and LAD2‐MCs. MCs were analyzed for the expression of CRY1 and OPN 1‐3 by qRT‐PCR and Western Blot as well as for the effects of irradiation with blue light on activation via IgE/anti‐IgE or cortistatin, a MRGPRX2 agonist. Results: We found expression of the blue light sensitive CRY1, OPN1 MW (medium‐wave‐length), OPN2 and OPN3 in LAD2‐MCs, cultured MCs from breast skin and foreskin as well as freshly isolated MCs from breast skin and eyelids, with the exception of OPN2 in eyelid MCs. CRY1 expression was the highest overall, and its presence was confirmed at protein level in cultured as well as freshly isolated MCs from breast skin and foreskin. PSCMCs, however, did not show expression of any of the investigated PRs. Importantly, fresh and cultured skin MCs were sensitive to blue light irradiation (at 453 nm) showing a dose‐dependent reduction in their degranulation after exposure to 2 or 30 J/cm2 blue light as measured by β‐hexosaminidase release. Conclusion: Our results demonstrate, for the first time, that human skin MCs express photoreceptors, i.e. CRY1 and OPN1‐3, and blue light, which activates these receptors, inhibits MC degranulation. These findings may explain, at least in part, circadian differences in allergic skin reactions and may be relevant for the development of photoreceptor‐targeted treatments for patients with MC‐driven skin diseases such as chronic spontaneous or inducible urticaria.