The effect of neuropeptides/hormones on Langerhans cells.

Neuropeptides/hormones have been shown to regulate the various functions of many immunocompetent cells. A number of neuropeptides/hormones has been demonstrated to be present in the skin and a close anatomical association between calcitonin gene-related peptide (CGRP)-containing nerves and Langerhans cells (LC) has been reported. In addition to the CGRP receptor, receptors for several neuropeptides including pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing peptide (GRP) are found on LC, suggesting these neuropeptides might have some effects on LC. CGRP inhibits alloantigen presentation and stimulation of a specific-antigen responsive T-cell clone by LC. Pre-treatment of LC with CGRP also inhibits the elicitation of delayed type hypersensitivity (DTH) in tumor immune mice. Upregulation of B7-2 expression on LC is suppressed by CGRP, which might be, in part, responsible for the inhibitory effect of CGRP in the functional assay. The production of some inflammatory cytokines such as IL-10 by LC-like cell line XS52 is regulated by CGRP and the functional effect of CGRP appears to be at least partially mediated through the autocrine regulation of IL-10. Alpha-MSH is another neuropeptide, the effect of which has been well studied in the cutaneous immune system. Pre-treatment of mice with alpha-MSH produces inhibitory effects in contact hypersensitivity (CHS). IL-10 has been suggested to be involved in the inhibitory effect of alpha-MSH. The receptors and the functional effects of other proopiomelanocortin (POMC)-derived peptides including beta-endorphin and catecholamines on LC are under investigation.