THE EFFECTS OF IL-20 SUBFAMILY CYTOKINES ON RECONSTITUTED HUMAN EPIDERMIS SUGGEST POTENTIAL ROLES IN CUTANEOUS INNATE DEFENSE AND PATHOGENIC ADAPTIVE IMMUNITY IN PSORIASIS.

This study by researchers at Genentech demonstrated that MatTek’s EpiDerm human skin tissue equivalent can be used to study the immunopathology of psoriasis. IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, researchers at Genentech show that primary human keratinocytes (KCs) express receptors for these cytokines, and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in EpiDerm reconstituted human epidermis (RhE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in reconstituted human epidermis (RhE), inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on EpiDerm cultured reconstituted human epidermis (RhE) treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.

Acanthosis, Beta-defensins, Cutaneous innate defense, EpiDerm, Epithelial cells, Hypogranulosis, IL-10 family of cytokines, IL-19, IL-20, IL-20 subfamily cytokines, IL-22, IL-24, IL-26, Immunopathology of psoriasis, Inflammation, Inflammatory, Inflammatory response, Kallikreins, Nuclear localization, Pathogenic adaptive immunity, Primary human keratinocytes, Psoriasis, Psoriasis-associated keratin 16, Psoriasis-associated protein S100A7, Psoriatic skin, Receptor complex R1 subunits, Reconstituted human epidermis (RHE), S100 family proteins, Stat3, Wound healing re-epithelialization