Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide

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Abstract
SEVERAL observations suggest interactions between the immune and nervous systems1,2. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation2. Neurotransmitters affect lymphocyte function1–4 and lymphoid organs are innervated5–9. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator10 that modulates some macrophage functions, including antigen presentation in vitro11. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation12, is present in epidermal nerves and is associated with Merkel cells10,13–15. We examined the ability of CGRP to modulate LC antigen-presenting function16 and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.