ARTICLE: Evolution of Skin Barrier Science for Healthy and Compromised Skin

April 2021 | Volume 20 | Issue 4 | Supplement Individual Articles | s3 | Copyright © April 2021


Published online April 6, 2021

Marek Haftek MD PhDa, Daniel C. Roy PhDb, I-Chien Liao PhDb

aCNRS UMR5305 LBTI - Laboratory for Tissue Biology and Therapeutic Engineering, Lyon, France
bL’Oréal Research and Innovation, Clark, NJ

Abstract
Skin is a complex organ comprised of multiple cell types and microstructures that work in concert to serve critical functions and support the body’s homeostasis. It is the outermost, cornified layer of our body that is primarily responsible for the permeability barrier, protecting against external aggressors and preventing water loss from within. The understanding of the organization, functionality, and underlying mechanisms of the skin barrier has evolved greatly through the years. The formation of an intact and well-maintained stratum corneum (SC), where the permeability barrier resides, relies heavily on the differentiation of epidermal keratinocytes and the synthesis, release, localization, and binding of lipids that include principally ceramides, cholesterol, and free fatty acids. The in-depth research on SC barrier, its disruption in the pathogenesis of diseases, as well as on barrier responses to environmental insults, has enabled the development of modern therapeutics and topical care routines. Among them, ceramide-containing moisturizers have clinically demonstrated the ability to support the management of skin conditions such as atopic dermatitis and psoriasis by reducing the disease severity and recurrence and improving the patients’ perception of overall skin quality and health. This review focuses on the contributions of various barrier constituents to skin barrier function in health and pathological conditions, and how topical interventions containing essential barrier lipids support barrier restoration and provide relief.

J Drugs Dermatol. 20(4 Suppl):s3-9. doi:10.36849/JDD.S589A

INTRODUCTION

Organization and Function of Epidermis Providing an Efficient Skin Barrier
The epidermis maintains its homeostasis and serves critical functions through a dynamic, self-renewing process in which the basal keratinocytes divide and migrate through the stratum spinosum and granulosum while progressively differentiating (Figure 1). When the keratinocytes reach the top of the granular layer, the process of terminal differentiation occurs in which the keratinocytes undergo programmed cell death and flatten out to form the stratum corneum (SC).1 During this process, the lamellar bodies of granular layer keratinocytes merge with the plasma membranes and release their predominantly lipid contents into the intercellular spaces of the nascent horny layer. An interplay of hydrolytic enzymes and their inhibitors, also excreted via the lamellar bodies, participate in elaboration of the intercellular layered lipid structure and, ultimately, are involved in cell desquamation at the top of the skin.2 Simultaneous to the extracellular lipid build-up, important changes occur within the keratinocytes upon the formation of SC. Transglutaminase-1 –mediated cross-linking of cytoplasmic proteins at the cell periphery results in the formation of highly insoluble cornified envelopes of the SC cells, thereafter called corneocytes.3 It is followed by a covalent binding to these structures of a monolayer of ceramides, replacing phospholipid plasma membranes of the living cells. These newly formed cornified lipid envelopes constitute the scaffold for further stacking and organization of the intercellular lipids. The composite structure of the SC, made of corneocytes intercalated by polar lipids, can be compared to a brick and mortar wall constituting SC permeability barrier.4

In order to perform its function as a permeability barrier, the epidermis must remain mechanically resistant while sufficiently flexible to accommodate skin movements and the treadmill-like flow of keratinocytes through the successive layers. Cell-cell and cell-substrate junctions play central roles in the maintenance of mechanical properties of the epidermis. Desmosomes, which interconnect individual cell cytoskeletons into a superstructure, evolve throughout the epithelial tissue, and change their location, protein composition, and glycan distribution according to the stage of the cell differentiation and the occurrence of mechanical constraints.5–7 In this process, actin cytoskeleton-bound adherens junctions participate in the dynamics of desmosome and tight junction expression. Upon the SC formation, these junctions become cross-linked to cornified envelopes and contribute to the enhanced physical resistance of the functional SC barrier.8 Mechanical properties of the SC show a significant increase in stiffness between the deep and superficial corneocytes.9 The mechanical integrity of the SC also depends on the direction of the applied shearing forces since lateral, side to side adhesion between the cells is stronger compared to that between the successive corneocyte layers.9–12