NEUROPEPTIDES IN THE SKIN - INTERACTIONS BETWEEN THE NEUROENDOCRINE AND THE SKIN IMMUNE-SYSTEMS

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increas ing attention. It has been observed that certain skin diseases such as psoriasis and atopic dermatitis have a neurogenic component. Neuropep tides released by sensory nerves that innervate the skin and often con tact epidermal and dermal cells can directly modulate functions of ker atinocytes, Langerhans cells (LC), mast cells, dermal microvascular en dothelial cells and infiltrating immune cells, Among these neuropeptid es the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) have been reported to effectively modulate skin and immune cell functions such as cell proliferation, cytokine production or antigen presentation under physiological or pathophysiological con ditions. Expression and regulation of their corresponding receptors th at are expressed on a variety of skin cells as well as the presence of neuropeptide-specific peptidases such as neutral endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final biological response mediated by these peptides on the target cell or tissue. Like wise, skin cells like keratinocytes or fibroblasts are a source for ne urotrophins such as nerve growth factor that are required not only for survival and regeneration of sensory neurons but also to control resp onsiveness of these neurons to external stimuli. Therefore, neuropepti des, neuropeptide receptors, neuropeptide-degrading enzymes and neurot rophins participate in a complex, interdependent network of mediators that modulate skin inflammation, wound healing and the skin immune sys tem. This review will focus on recent studies demonstrating the role o f tachykinins, CGRP. SOM and VIP and their receptors and neuropeptide- degrading enzymes in mediating neurogenic inflammation in the skin.