Calcitonin gene-related peptide and Langerhans cell function

Morphologic studies have indicated that Langerhans cells (LC) are frequently in anatomic apposition with epidermal nerves containing the neuropeptide calcitonin gene-related peptide (CGRP). Experiments were undertaken to examine whether CGRP modulates LC function. The effect of pre-exposure of LC to CGRP in vitro on alloantigen presentation and specific protein presentation to a responsive T-cell line were studied using freshly prepared murine epidermal cell populations enriched for LC content (EC) by treatment with antibody to Thy-1 and complement. The ability of EC to present tumor-associated antigens for induction and elicitation of delayed-type hypersensitivity (DTH) in tumor-immune mice was also examined. Inhibitory effects of CGRP on antigen presentation were observed in each of these assays. Experiments were also performed examining the ability of intradermally administered CGRP to modulate induction of contact hypersensitivity (CHS) to a hapten applied at the injected site. Administration of CGRP led to a decrease in the CHS response after immunization at the site of injection. Intracellular cAMP was significantly increased in freshly prepared LC after exposure to CGRP, and this process could be inhibited by a specific inhibitor of the CGRP receptor, demonstrating the existence of CGRP receptors on LC. B7-2 expression induced by LPS and GM-CSF in the LC-like line XS52, and by LPS in peritoneal macrophages, was suppressed by CGRP. This suppression may account, in part, for the inhibitory effect of CGRP. As a whole, these observation suggest that regulation of antigen presentation by nerves may occur in the epidermis.