Epidermis

The human skin is one of the largest organs in the body. It accounts for ∼8 % of an adult's body mass and covers a surface area of approximately 25^m2 if the surface area of ∼5 million appendages (hair follicles and sweat ducts) is taken into account.

The epidermis is supported by the dermis, a network of fibrils, blood vessels, pilosebaceous units, sweat glands, nerves and cells. The skin in its entirety is a protective shield against numerous harmful influences, including microorganisms and chemical and physical factors. These functions depend on the activity of numerous growth factors, peptide hormones, proteases and specific signaling pathways that are triggered by the activation of different types of receptors in the cell membranes of the various cell types of the skin.

The thickness of the epidermis varies between 0.04 mm (eyelids) and 1.5 mm (palms and soles). The epidermis is of ectodermal origin and consists of about 90% keratinocytes and sits on a basal lamina. It is interspersed with symbiotic cells, e.g. melanocytes, Langerhans cells, Merkel cells. The keratinocytes (size approx. 30 μm) develop in the basal cell layer, migrate through the epidermis and differentiate into devitalized horny cells ( corneocytes). The individual epidermal layers are referred to as:

• Stratum basale
• stratum spinosum
• stratum granulosum
• stratum lucidum
• stratum corneum.

The transit time through the stratum spinosum takes about 14 days. The renewal time of the stratum corneum also lasts 14 days. The stratum corneum has an important barrier function. The keratinocytes of the epidermis organize themselves into a variable number of cell layers, which are finally differentiated when they reach the epidermal surface; at this point, the cored, dead cells of the stratum corneum are continuously shed and replaced by new, finally differentiated keratinocytes. As part of the differentiation process, keratinocytes change their morphological appearance and begin to express specific protein markers such as the cytokeratins CK1 and CK10, (pro-) filaggrin, type I transglutaminase, involucrin and loricrin, which indicate the state of differentiation they are in. Mutations in the genes encoding these proteins lead to the development of human skin diseases (e.g. mutations in the filaggrin gene lead to ichthyosis vulgaris) (Smith FJD et al. 2006). The epidermis is one of the most extensive epithelial surfaces that protects the host from attack by pathogens while maintaining a peaceful coexistence with its local microbiome, allowing microbes to influence skin homeostasis. Part of the defense mechanism against invading organisms relies on an acidic epidermal surface, which is also associated with the regulation of several critical proteases responsible for maintaining healthy skin (Ali SM et al. 2013).

The sawtooth-like boundary zone between the epidermis and dermis is called the dermoepidermal junction zone. The extensions of the epidermis into the dermis are called rete ridges, the dermal protrusions in between are called dermal papillae.

As a defense barrier, keratinocytes are important modulators of the innate and adaptive immune response. For example, keratinocytes express Fc receptors (FcγRI, FcγRII and FcγRIII), complement receptors and mannose receptors, which enable them to kill a variety of microorganisms. In addition, keratinocytes also express Toll-like receptors (TLRs) 1 to 10, some of which can be upregulated by certain microorganisms, products derived from them or inflammatory diseases of the skin such as varicella-zoster virus infection, atopic dermatitis and psoriasis (Gutowska-Owsiak D et al. 2012).

Furthermore, keratinocytes are a rich source of cytokines, chemokines and antimicrobial peptides of the defensin or cathelicidin family, which influence the performance of neutrophils and macrophages in wound healing.

The various components of the kallikrein, kinin families and kallikrein-related peptidases (KLKs) have been shown to modulate essential skin functions, including cell desquamation, activation of antimicrobial peptides and keratinocyte differentiation, events that are important in the pathogenesis and/or maintenance of certain chronic skin diseases (Nauroy P et al. 2020). Desquamation of superficial keratinocytes depends on the hydrolysis of desmosomal compounds by specific proteases (kallikrein-related peptidases KLKs) (Chen JQ et al. 2019).

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