Updated Perspectives on Keratinocytes and Psoriasis: Keratinocytes are More Than Innocent Bystanders.
Updated Perspectives on Keratinocytes and Psoriasis: Keratinocytes are More Than Innocent Bystanders.
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DOI：
10.2147/ptt.s327310
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发表时间：
2022
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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至关重要。牛皮癣的发病机制是什么？在这种疾病中，角质形成细胞的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激发银屑病中观察到的炎症反应中的作用。除了免疫细胞，越来越多的证据表明，角质形成细胞参与银屑病的发病机制，如本文所讨论的。虽然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以产生可促进其增殖的抗微生物肽、细胞因子和趋化因子，以及募集免疫细胞以帮助启动和加强炎症反馈回路。银屑病角质形成细胞甚至在从体内炎症环境中去除后也显示出与正常角质形成细胞的内在差异;因此，已经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，这些变化有助于银屑病。Koebner现象，其中损伤促进银屑病病变的发展，也为角质形成细胞在疾病发病机制中的作用提供了证据。此外，转基因小鼠研究证实了角质形成细胞在银屑病病因中的重要性。最后，除了免疫细胞和角质形成细胞，文献中的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。这些其他贡献者都是治疗的潜在目标，这表明在治疗银屑病时采用整体方法的重要性。
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.