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 TNFα and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNFα 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 TNFα, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNFα, 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.

中文翻译：

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角质形成细胞中 TNFα、IL-17A 和 EGF 对 IL-23 的协同诱导

IL-23 是一种炎性细胞因子，通过增强 Th17 细胞增殖和存活以及 Th17 细胞因子的产生，在 Th17 免疫中发挥重要作用。IL-23 在包括银屑病在内的 Th17 介导的炎症性疾病的发展中具有致病作用。尽管通过阻断 IL-23 成功治疗了银屑病，但银屑病患者中 IL-23 表达的调节在很大程度上是未知的。树突状细胞通常被认为是银屑病中 IL-23 的主要来源。虽然在银屑病表皮中发现了高水平的 IL-23，但在银屑病角化眼中 IL-23 的表达仍然是一个有争议的问题。在这项研究中，我们证明了 IL-23 的产生是由人角质形成细胞中的 TNFα 和 IL-17A 的组合诱导的。此外，这种由 TNFα 和 IL-17A 诱导的 IL-23 在银屑病角质形成细胞中进一步增加，并通过 EGFR 信号传导增强。尽管树突状细胞和巨噬细胞中的 toll 样受体激动剂也强烈诱导 IL-23，但这些细胞类型中的 IL-23 表达不受 TNFα、IL-17A 和 EGFR 信号传导的调节。鉴于 IL-23 对于维持 Th17 活化至关重要，角质形成细胞中 TNFα、IL-17A 和 EGF 对 IL-23 的诱导可能在银屑病发病机制以及与 EGFR 抑制治疗相关的皮疹中发挥重要的病理作用。