How to Build and Regenerate a Functional Skin Barrier: The Adhesive and Cell Shaping Travels of a Keratinocyte.

In this perspective, we focus on the skin epidermis and take you on a journey that highlights the adhesive- and cell shape‒changing adventures of a keratinocyte while it travels through the different layers of the epidermis, which is essential to make, maintain, and repair this barrier.

Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8.

Antimicrobial peptides (AMPs) are the body's natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon understanding the regulatory mechanisms governing their unconventional secretion from cells. Analysis of the secretion of S100A7 (Psoriasin), an abundant AMP stored in differentiated keratinocytes of the skin, has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1, and interleukin (IL)-1α. The initial activation of this core machinery is mediated by Toll-like receptor signaling, whereas the chronic response is mediated by Caspase-8 downregulation. Interestingly, there is a concomitant downregulation of Caspase-8 in inflammatory skin diseases wherein S100A7 is constitutively released. These results highlight the potential of targeting these components to control the release of AMPs from the skin in both homeostatic and disease conditions.