Calcitonin Gene-Related Peptide and its Influences on the Cutaneous Immune System

Much evidence indicates that nerves can influence the cutaneous immune system. One key player in these interactions is calcitonin gene-related peptide (CGRP). CGRP has complex regulatory effects on epidermal Langerhans cells in vitro. These include inhibition of antigen presentation for Th1-type immunity and enhancement of presentation for Th2 and Th17-type responses. CGRP inhibits the ability of murine Langerhans cells to present tumor-associated antigens for induction of immunity in naive mice or elicitation of immunity in pre-immunized mice. Administration of CGRP intradermally into naive mice inhibits induction of immunity to Th1-dominant haptens at the injected site while augmenting immunity to Th2-dominant haptens. CGRP also inhibits the stimulated production of some chemokines by human dermal microvascular endothelial cells (ECs) and, accordingly, inhibits the ability of stimulated ECs to chemoattract neutrophils or peripheral blood mononuclear cells. Administered in vivo, CGRP can inhibit inflammation in several models. Furthermore, there is some evidence that CGRP is involved in pathologic states including psoriasis, atopic dermatitis, HIV-1 infection, and ultraviolet radiation-induced immunosuppression. A greater understanding of CGRP regulation of cutaneous immunobiology may have important implications for the development of novel approaches to prevent or treat skin disorders involving inappropriate or unwanted activities of the immune system.