Divison of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Front Immunol. 2023 May 22;14:1186455. doi: 10.3389/fimmu.2023.1186455. eCollection 2023.
Psoriasis is a common chronic inflammatory skin disease, associated with substantial comorbidity. TH17 lymphocytes, differentiating under the influence of dendritic cell-derived IL-23, and mediating their effects IL-17A, are believed to be central effector cells in psoriasis. This concept is underlined by the unprecedented efficacy of therapeutics targeting this pathogenetic axis. In recent years, numerous observations made it necessary to revisit and refine this simple "linear" pathogenetic model. It became evident that IL-23 independent cells exist that produce IL-17A, that IL-17 homologues may exhibit synergistic biological effects, and that the blockade of IL-17A alone is clinically less effective compared to the inhibition of several IL-17 homologues. In this review, we will summarize the current knowledge around IL-17A and its five currently known homologues, namely IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25) and IL-17F, in relation to skin inflammation in general and psoriasis in particular. We will also re-visit the above-mentioned observations and integrate them into a more comprehensive pathogenetic model. This may help to appreciate current as well as developing anti-psoriatic therapies and to prioritize the selection of future drugs' mode(s) of action.
银屑病是一种常见的慢性炎症性皮肤病，与多种合并症相关。TH17 淋巴细胞在树突状细胞衍生的 IL-23 的影响下分化，并通过 IL-17A 介导其作用，被认为是银屑病的核心效应细胞。这一概念被靶向该发病轴的治疗方法前所未有的疗效所强调。近年来，许多观察结果使得有必要重新审视和完善这一简单的“线性”发病模型。很明显，存在不依赖于 IL-23 的细胞，这些细胞产生 IL-17A，IL-17 类似物可能表现出协同的生物学效应，并且与抑制几种 IL-17 类似物相比，单独阻断 IL-17A 在临床上的效果较差。在这篇综述中，我们将总结目前关于 IL-17A 及其五个目前已知的类似物（即 IL-17B、IL-17C、IL-17D、IL-17E（也称为 IL-25）和 IL-17F）在一般皮肤炎症和特别是银屑病中的相关知识。我们还将重新审视上述观察结果，并将其整合到一个更全面的发病模型中。这有助于了解当前和正在开发的抗银屑病疗法，并优先选择未来药物的作用模式。
