Is MC1 dispensable for regulation of cutaneous inflammatory and immune responses?

The melanocortin-1 receptor (MC1 ) - being most abundantly expressed in the skin by melanocytes - has a physiological role for melanin pigmentation in many vertebrate species. MC1 has also been implicated in regulation of skin inflammation as this receptor is detectable in the majority of non-melanocytic cell types and its ligand α-melanocyte-stimulating hormone (α-MSH) exerts immunoregulatory and anti-inflammatory effects. However, in vivo studies on mice with targeted disruption of MC1 have been missing in the context of skin inflammation until recently. Wolnicka-Glubisz et al. now reported that the course of ultraviolet (UV)-induced inflammation, contact hypersensitivity, neonatal immune tolerance and UV-induced immunosuppression is similar in MC1 signal-deficient (C57BL/6-Mc1r(e/e)) and wild-type mice. These unexpected findings are supported by own observations in experimentally induced immune-complex-mediated vasculitis: Mc1r(e/e) mice exhibited a similar extent of the reverse passive cutaneous Arthus reaction compared with wild-type animals. Future studies are thus needed to clarify whether these findings are due to limitations in the chosen mouse model and/or point to additional MC subtypes that may regulate inflammatory and immune responses in the skin.