Schwann cells as underestimated, major players in human skin physiology and pathology

Abstract

Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor‐like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial‐to‐mesenchymal‐like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.

Thermal Pain Thresholds Are Significantly Associated with Plasma Proteins of the Immune System in Chronic Widespread Pain—An Exploratory Pilot Study Using Multivariate and Network Analyses

“…Dys-regulation in the bidirectional signalling between the nociceptive and immune systems may be associated with excitation [72]. The nociceptors are in direct association or near association with nociceptive Schwann cells in the epidermis and form a mesh-like network [73,74]. The intimate bidirectional relationships between the immune system and the nociceptors peripherally may indicate priming of the immune system [75].…”

Recent progress at the psoriasis and atopic dermatitis research front: An experimental dermatology perspective

“…Typically, SCs tend to be ignored in the context of immunodermatology. Recently, however, it has been argued that repeated activation of the SC repair programmes that are routinely recruited during wound healing may contribute to the pathogenesis of AD and PSO 60 . If confirmed by future studies, this would mean that SCs must come into the focus of mainstream immunodermatology research.…”

“…Schwann cells (SCs) are neural crest‐derived cells that support neuronal axons by producing the myelin sheath, and SCs also support neuron axonal regeneration during skin wound repair 60 . Typically, SCs tend to be ignored in the context of immunodermatology.…”

MRGPRX2 signals its importance in cutaneous mast cell biology: Does MRGPRX2 connect mast cells and atopic dermatitis?

“…Additional elements of this unit like Schwann cells could further contribute to pathology. [ 82 ] In other manifestations of the disease, such as extrinsic and/or strongly Th2‐dependent forms, MRGPRX2 may rather act as a bystander (in analogy with the suggested bystander role of FcεRI, especially in intrinsic AD). This is supported by our finding that IL‐4 dampens and does not strengthen the MRGPRX2‐route in skin MCs (Table 1).…”