Ortiz-Lopez Laura I, Choudhary Vivek, Bollag Wendy B
Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Psoriasis (Auckl). 2022 May 2;12:73-87. doi: 10.2147/PTT.S327310. eCollection 2022.
Psoriasis is a complex disease triggered by genetic, immunologic, and environmental stimuli. Many genes have been linked to psoriasis, like the psoriasis susceptibility genes, some of which are critical in keratinocyte biology and epidermal barrier function. Still, the exact pathogenesis of psoriasis is unknown. In the disease, the balance between the proliferative and differentiative processes of keratinocytes becomes altered. Multiple studies have highlighted the role of dysregulated immune cells in provoking the inflammatory responses seen in psoriasis. In addition to immune cells, accumulating evidence shows that keratinocytes are involved in psoriasis pathogenesis, as discussed in this review. Although certain immune cell-derived factors stimulate keratinocyte hyperproliferation, activated keratinocytes can also produce anti-microbial peptides, cytokines, and chemokines that can promote their proliferation, as well as recruit immune cells to help initiate and reinforce inflammatory feedback loops. Psoriatic keratinocytes also show intrinsic differences from normal keratinocytes even after removal from the in vivo inflammatory environment; thus, psoriatic keratinocytes have been found to exhibit abnormal calcium metabolism and possible epigenetic changes that contribute to psoriasis. The Koebner phenomenon, in which injury promotes the development of psoriatic lesions, also provides evidence for keratinocytes' contributions to disease pathogenesis. Furthermore, transgenic mouse studies have confirmed the importance of keratinocytes in the etiology of psoriasis. Finally, in addition to immune cells and keratinocytes, data in the literature support roles for other cell types, tissues, and systems in psoriasis development. These other contributors are all potential targets for therapies, suggesting the importance of a holistic approach when treating psoriasis.
银屑病是一种由遗传、免疫和环境刺激引发的复杂疾病。许多基因与银屑病有关，如银屑病易感基因，其中一些在角质形成细胞生物学和表皮屏障功能中起关键作用。然而，银屑病的确切发病机制尚不清楚。在该疾病中，角质形成细胞增殖和分化过程之间的平衡被改变。多项研究强调了免疫细胞失调在引发银屑病中所见炎症反应中的作用。除免疫细胞外，越来越多的证据表明角质形成细胞参与了银屑病的发病机制，本文将对此进行讨论。尽管某些免疫细胞衍生因子刺激角质形成细胞过度增殖，但活化的角质形成细胞也可产生抗菌肽、细胞因子和趋化因子，这些物质可促进其增殖，并募集免疫细胞以帮助启动和加强炎症反馈回路。即使从体内炎症环境中移除后，银屑病角质形成细胞与正常角质形成细胞相比仍表现出内在差异；因此，已发现银屑病角质形成细胞表现出异常的钙代谢和可能的表观遗传变化，这些变化促成了银屑病。同形反应（即损伤促进银屑病皮损的发展）也为角质形成细胞对疾病发病机制的贡献提供了证据。此外，转基因小鼠研究证实了角质形成细胞在银屑病病因学中的重要性。最后，除免疫细胞和角质形成细胞外，文献数据支持其他细胞类型、组织和系统在银屑病发展中的作用。这些其他促成因素都是治疗的潜在靶点，这表明治疗银屑病时采用整体方法的重要性。
