Nerve-derived transmitters including peptides influence cutaneous immunology

Abstract

Clinical observations suggest that the nervous and immune systems are closely related. For example, inflammatory skin disorders; such as psoriasis, atopic dermatitis, rosacea and acne; are widely believed to be exacerbated by stress. A growing body of research now suggests that neuropeptides and neurotransmitters serve as a link between these two systems. Neuropeptides and neurotransmitters are released by nerves innervating the skin to influence important actors of the immune system, such as Langerhans cells and mast cells, which are located within close anatomic proximity. Catecholamines and other sympathetic transmitters that are released in response to activation of the sympathetic nervous system are also able to reach the skin and affect immune cells. Neuropeptides appear to direct the outcome of Langerhans cell antigen presentation with regard to the subtypes of Th cells generated and neuropeptides induce the degranulation of mast cells, among other effects. Additionally, endothelial cells, which release many inflammatory mediators and express cell surface molecules that allow leukocytes to exit the bloodstream, appear to be regulated by certain neuropeptides and transmitters. This review focuses on the evidence that products of nerves have important regulatory activities on antigen presentation, mast cell function and endothelial cell biology. These activities are highly likely to have clinical and therapeutic relevance.

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

“…In a nutshell, these studies mirror observations in other barrier tissues in that Substance P is pro-inflammatory, whereas CGRP has anti-inflammatory properties [87]. We refer the interested reader to the original literature and comprehensive reviews on this topic [87, 176, 181–184]. …”

“…In addition to PRR signaling, DCs and other myeloid leukocytes integrate signals from neuropeptide, which can influence cytokine profiles [87] (Figure 2). The pro-inflammatory activities of substance P were first mechanistically linked to enhanced production of IL-1, TNF-α, and IL-6 by monocytes [88].…”

Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics

“…TRP and PGE2 can exhibit mutually enhanced function in the presence of one another, resulting in a lower threshold for TRP activation and increased pain sensation . Mast cell activation by neuropeptides can result in the release of histamine, which may influence vasodilation; tryptase, a chemotactic agent for fibroblasts; and MMP . Both fibroblasts and MMP have been implicated in fibrotic processes in rosacea skin and are surprisingly present in even the earliest stages of rosacea .…”

Assessment of sympathetic skin response to acne vulgaris

“…The authors suggested that this may be due to changes in the epithelial melanocyte system as a responsible mechanism [3]. Apart from α-MSH melanogenesis, pilosebase is involved in the inflammatory and immune response of the unit [13]. Increased α-MSH and MC-1R expression in sebaceous glands has been shown in patients with acne in the case of systemic or cutaneous stress.…”