Soluble mediators in the function of the epidermal-immune-neuro unit in the skin

Abstract

Skin is the largest, environmentally exposed (barrier) organ, capable of integrating various signals into effective defensive responses. The functional significance of interactions among the epidermis and the immune and nervous systems in regulating and maintaining skin barrier function is only now becoming recognized in relation to skin pathophysiology. This review focuses on newly described pathways that involve soluble mediator-mediated crosstalk between these compartments. Dysregulation of these connections can lead to chronic inflammatory diseases and/or pathologic conditions associated with chronic pain or itch.

Potential Role of the Skin in Hypertension Risk Through Water Conservation

“…The skin serves as a sensory organ that detects external stimuli and transmits information regarding these, acts as a barrier to prevent invasion by bacteria and other organisms, and regulates body temperature through heat exchange with the external environment. [16][17][18] In addition, the skin synthesizes vitamin D and helps regulate circadian rhythms through photosensitivity. 19,20 In this review, we focus on the barrier function of the skin with respect to water conservation.…”

Role of neurogenic inflammation in the pathogenesis of alopecia areata

“…Activated TRPV1 channels lead to calcium flux into the intracellular space, and the cell subsequently releases neuropeptides. 32 Neuropeptides innervate the surface blood vessels of the skin and lead to enhanced vascular permeability and plasma exosmosis, and deliver pro-inflammatory mediators by promoting the upregulation of receptor-dependent intercellular adhesion molecules and vascular cell adhesion molecules. Furthermore, the activation of mast cells results in their degranulation and the subsequent release of plenty mediators, including proteases, cytokines, and histamines.…”

Neural Regulation of Innate Immunity in Inflammatory Skin Diseases

“…The skin comprises three major layers: epidermis, dermis, and subcutis [ 10 ]. The cutaneous immune cells mainly reside in the epidermis and dermis, where they are more likely to encounter environmental invaders.…”

“…Antigen-presenting cells, including Langerhans cells and dermal dendritic cells (DCs), serve as part of the first line of defense against pathogens. Langerhans cells are often restricted to the epidermis, while dermal DCs stay deeper in the skin, and both of them are found in close proximity to nerve fibers [ 10 , 11 ]. Unlike mast cells that are usually skin-resident in the steady state, other myeloid cells, such as basophils, eosinophils, and neutrophils, are commonly found in the dermis in skin inflammatory conditions [ 12 , 13 ].…”

“…Histopathologic examination of skin lesions in patients with psoriasis revealed that, compared with non-pruritic skin tissues, the pruritic areas had more mast cells and degranulated mast cells [ 69 ]. Additionally, a rich innervation of nerves and an increase in SP-, CGRP-, and VIP-positive nerve fibers were also shown in the psoriatic skin [ 10 ]. In addition, there is a greater frequency of morphological contacts between neurofilament+ nerves and tryptase+ mast cells in psoriatic lesions than in non-lesional skin or normal-looking skin, suggesting a morphologic basis for mast cell–neural interactions in this disease [ 70 ].…”