Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Semin Cell Dev Biol. 2022 Aug;128:112-119. doi: 10.1016/j.semcdb.2021.06.018. Epub 2021 Jul 3.
Keratin 17 (K17) is a multifaceted cytoskeletal protein that is not commonly expressed in the epidermis under normal physiological conditions. However, in psoriasis, K17 is overexpressed in the suprabasal layer of the epidermis and plays an important role in the pathogenesis of the disease. In this review, we have summarized our findings and those reported in other studies concerning the pathogenic functions of K17, as well as the mechanisms underlying the increase in K17 expression in psoriasis. K17 exerts both pro-proliferative and pro-inflammatory effects on keratinocytes. Moreover, K17 peptides trigger autoreactive T cells and promote psoriasis-related cytokine production. In turn, these cytokines modulate the expression, stability, and protein-protein interactions of K17 through transcriptional and translational regulation and post-translational modification of K17 in keratinocytes. Thus, a K17/T-cell/cytokine autoimmune loop is implicated in the pathogenesis of psoriasis, which is supported by the fact that therapies targeting K17 have achieved good outcomes in psoriasis-like mouse models. Future perspectives of K17 in psoriasis have also been discussed to provide potential directions for further studies.
角蛋白 17（K17）是一种多功能细胞骨架蛋白，在正常生理条件下通常不会在表皮中表达。然而，在银屑病中，K17 在表皮的基底上层过度表达，在疾病的发病机制中发挥重要作用。在这篇综述中，我们总结了我们的发现以及其他研究报告的关于 K17 的致病功能，以及 K17 在银屑病中表达增加的机制。K17 对角质形成细胞具有促有丝分裂和促炎作用。此外，K17 肽触发自身反应性 T 细胞并促进与银屑病相关的细胞因子产生。反过来，这些细胞因子通过角质形成细胞中转录和翻译调节以及 K17 的翻译后修饰来调节 K17 的表达、稳定性和蛋白-蛋白相互作用。因此，K17/T 细胞/细胞因子自身免疫环参与了银屑病的发病机制，这一事实得到了支持，即针对 K17 的治疗方法在类银屑病小鼠模型中取得了良好的效果。还讨论了 K17 在银屑病中的未来展望，为进一步研究提供了潜在方向。
