Basics of skin barrier function

The stratum corneum corresponds to the outermost layer of the epidermis and is largely responsible for the barrier function establishment. Until the seventies, the stratum corneum, which is composed of dead and flattened ‘mummified’ cells called corneocytes, was thought to be biologically inert. In the late seventies and in the eighties emerged the important concept of barrier function with the model of the ‘brick wall’ proposed by Peter Elias. In this model, the corneocytes were the bricks, embedded within an intercellular lipid substance, which was the mortar, considered responsible for cell cohesion. Since then many other actors have been found to contribute significantly to the formation of the epidermal barrier. Among these factors, tight junctions, cohesion structures including desmosomes and corneodesmosomes, scaffolding proteins (involucrin/envoplakin/ periplakin), filaggrin, proteases, proteases inhibitors and antimicrobial peptides all play an important role in maintaining barrier function. This review will cover all these components and how important they are to provide adequate barrier function. Thus, we will show how sophisticated is the cutaneous barrier function and that a better understanding of how it takes place, is essential to develop new cosmetic actives with skin-barrierreinforcing properties.

 The skin is the largest organ of the body. It has three main layers, the epidermis (a multilayered waterproof epithelium), the dermis (a connective tissue) and the subcutaneous fat layer. Our skin is a vital organ that corresponds to the interface between our body and the external environment. Among its many functions, the protective barrier against mechanical, thermal and physical injury and hazardous substances is one of the most important. Moreover, the skin is essential to prevent loss of moisture and limit harmful effects of UV radiation. Additionally, the skin acts as a sensory organ. In fact, it contains many nerve fibres that are essential for the perception of various external stimuli. Finally, the skin has thermoregulatory and immunological functions, and it is involved in the vitamin D synthesis when exposed to sunlight. The epidermis is the uppermost layer of the skin and is composed largely of keratinocytes (so named because they express a high amount of intermediate filament proteins: the keratins). The epidermis plays an important role in the formation of the skin barrier function. Indeed, it is considered that this barrier resides mainly in the outermost layer of the epidermis, the cornified layer or stratum corneum (SC) (also known as the horny layer).1,2 The epidermis possesses an important self-renewal capacity due to the presence of adult stem cells that are able to divide. These cells are located in the basal layer and provide new keratinocytes to replace the dead corneocytes, which are shed naturally in a complex process called desquamation (Fig. 1). Thanks to the presence of these adult stem cells, the epidermis renews itself approximately every 28 days in order to continuously maintain the barrier function. With their outward movement, the basal keratinocyte cease to divide and give rise to more differentiated cell layers such as the spinous layer, granular layer and the SC (Fig. 1). During the entire terminal epidermal differentiation programme, many proteins and factors are produced in order to ensure an effective functional barrier. The SC was initially described by Rothman S. as an amorphous mass lacking a cellular structure, constituted by a loose mass of keratin fibrils.3 It was regarded as an inert ‘basket weave’ of terminally differentiated flattened and enucleated cells surrounded by a cornified envelope. In the eighties and nineties, with the development of more sophisticated and powerful methodologies, the ultrastructural and components of the SC were largely characterised and permitted to investigate the SC properties and functions. Since then, many other factors have been identified to play an essential role in the establishment and the maintenance of epidermal barrier function.

Stratum corneum structure and function