INTRODUCTION
The skin has evolved a unique structure that is essential for survival; the stratum corneum (SC). The SC prevents excess water loss and forms a formidable barrier to the ingress of microorganisms and exogenous materials. Morphologically, the SC is comprised of corneocytes interspersed in lipid bilayers, the so called “brick and mortar model”.1 However, the analogy suggests that the SC is an inert, unchanging structure and fails to convey the extent to which metabolism and remodeling continue as the corneocytes transit from the base of the SC to the surface. The explosion in microbiome research has demonstrated that the SC harbors a rich diversity of microbes2 that form an additional barrier to the colonization of pathogens. Moreover, the microflora communicates with and directs the host immune system and can be considered an integral part of the skin’s immunity. The intimate association of microbes and skin is such that, perhaps, the bricks and mortar analogy should be updated to include skin’s microbiota as a third component, wherein the microbes form the shingles on the roof of a bricks and mortar house.Stratum Corneum Formation The epidermis has several distinct layers. At the dermal-epidermal junction sits the basal layer of proliferating keratinocytes. Within this layer reside both epidermal stem cells and transit amplifying cells that are destined to detach from the basement membrane and begin the process of terminal differentiation. As keratinocytes differentiate, they enlarge and progressively flatten. This progression is accompanied by a bewilderingly complex set of changes in the expression of specialized proteins and lipids. Terminal differentiation culminates in the transition of the granular layer cells to corneocytes, anucleate, and proteinaceous sacs, surrounded by a lipid envelope, and interspersed in lipid lamellae. This amazing conversion from viable keratinocyte to corneocyte occurs in a highly ordered fashion within the space of one cell layer, cued by mechanisms that are still not clearly understood (Figure 1). It is truly a remarkable transformation.Cornified Envelope Keratins are cytoskeletal proteins that form intermediate filaments and serve as the scaffolding for cornified envelope (CE) formation. Commitment to differentiation is evidenced by a switch to a predominance of K1 & K10 in the spinous layer where the synthesis of proteins, such as involucrin, also begins. In the granular layer, these proteins are crosslinked into the CE by the action of transglutaminases. Specialized lipids are secreted into the extracellular space and will form the lipid coat that surrounds each corneocyte, the cornified lipid envelope (CLE). The stratum granulosum (SG) is so-named because of the presence of keratohyalin granules (KHG) containing loricrin and small proline-rich proteins (SPR), which further reinforce the CE. KHGs also contain filaggrin. This protein aggregates keratin filaments and promotes the collapse of the keratinocyte. The lamellar granules (LG) are also extruded from granular cells releasing their precious cargo of lipids and proteins.As the keratinocyte transitions to a corneocyte, nuclei, intracellular organelles, and plasma membrane components are degraded. Desmosomes, the molecular rivets between adjacent keratinocytes, are converted to corneodesmosomes (CD) by the addition of corneodesmosin3 strengthening cell:cell adhesion. Maturation continues as the corneocyte transits through the SC. Crosslinking of proteins such as loricrin, trichohyalin, and SPRs into the CE continues and this facilitates the switch from a “fragile” to a “rigid” phenotype.4 In dry or photoexposed skin, the ratio of rigid:fragile in the outer SC is decreased indicat
