“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases

Abstract

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as “input cytokines”, and the produced cytokines as “output cytokines”. Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines.

A Platform for Testing the Biocompatibility of Implants: Silicone Induces a Proinflammatory Response in a 3D Skin Equivalent

“…In acute inflammation, IL-33, as an alarmin, is expressed in human keratinocytes in contrast to murine cells [37,41]. The significant rise in IL-33 concentration in our 3D skin equivalents with implants is thus not only indicative of the proinflammatory potential of silicone but demonstrates once more the importance of research platforms based on human cells such as the one introduced here, as this species-specific reaction could not be replicated in a murine model.…”

“…Keratinocytes as immunologically active barrier cells secrete various proinflammatory cytokines, among them being the cytokines we tested for in this study (IL-1 α, IL-6, IL-8, IL-33, MCP-1, and TNF-α) and with all of them showing statistically significant higher concentrations after addition of the silicone implant to our 3D skin equivalent [28,36,37]. Silicone has been shown to elevate the levels of monocyte secretion of IL-6 and TNFα in vitro [27].…”

Recombinant Fowlpox Virus fpIBD1 in Chicken’s Skin: Persistence and the Local Immune Response at the Site of Inoculation

“…The regulation of the entry of activated T and B lymphocytes into skin tissue is not well understood. There is also evidence that keratinocytes participate in immune responses in the skin since these cells produce a wide variety of cytokines that can modulate T cell responses [38].…”

The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment

“…Leucocytes, dendritic T cells, macrophages, mast cells, natural killer, and Langerhans cells are strategically disseminated along all epidermal layers [ 100 , 101 ]. Stratum corneum includes several microbial sensors such as Toll-like receptors, antimicrobial peptides, and cytokines produced physiologically and in response to microbial invasion [ 102 ].…”