Synergistic induction of IL-23 by TNFα , IL-17A, and EGF in keratinocytes

IL-23 is an inflammatory cytokine that plays an essential role in Th17 immunity by enhancing Th17 cell proliferation and survival, and Th17 cytokine production. IL-23 has pathogenic roles in the development of Th17-mediated inflammatory diseases including psoriasis. Despite successful treatment of psoriasis by blocking IL-23, the regulation of IL-23 expression in psoriasis patients is largely unknown. Dendritic cells are generally considered to be the primary source of IL-23 in psoriasis. While high levels of IL-23 are found in psoriatic epidermis, IL-23 expression in psoriatic keratinoctyes remains a controversial issue. In this study, we demonstrated that IL-23 production is induced by a combination of TNF alpha and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNF alpha and IL-17A is further increased in psoriatic keratinocytes and is enhanced by EGFR signaling. Although IL-23 is also robustly induced by toll-like receptor agonists in dendritic cells and macrophages, IL-23 expression in these cell types is not regulated by TNF alpha, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNF alpha, IL-17A, and EGF in keratinocytes could play an important pathological role in psoriasis pathogenesis as well as the cutaneous rash associated with EGFR inhibition therapy.

Automated summary

IL-23 plays a crucial role in Th17 immunity and inflammatory responses, especially in diseases like psoriasis. While dendritic cells are considered the main source of IL-23 in psoriasis, there is controversy surrounding the expression of IL-23 in psoriatic keratinocytes. Research has shown that a combination of TNF alpha and IL-17A can induce IL-23 production in human keratinocytes, with enhanced effects in psoriatic keratinocytes and EGFR signaling.