Lynderm Research Inc, Markham, Ontario, Canada.
Centre de Recherche Dermatologique du Quebec Metropolitain, Quebec City, Quebec, Canada.
J Am Acad Dermatol. 2014 Jul;71(1):141-50. doi: 10.1016/j.jaad.2013.12.036. Epub 2014 Mar 18.
Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis.
过去 30 年来，人们对银屑病发病机制的分子和细胞理解取得了长足的进展。早在 20 世纪 80 年代初，人们认为银屑病是一种由角质形成细胞过度增殖驱动的皮肤疾病。在接下来的 20 年里，免疫系统和辅助性 T 细胞（Th）在银屑病发病机制中的作用得到了认识。在银屑病皮损中存在白细胞介素（IL）-12 细胞因子，这导致了银屑病是由 Th1 细胞介导的假说。最近的证据揭示了 Th17 细胞和其他免疫细胞作为银屑病皮肤炎症的近端调节因子的作用。Th17 细胞的主要效应细胞因子 IL-17A 刺激角质形成细胞产生趋化因子、细胞因子和其他促炎介质，从而使 IL-17A 能够连接先天和适应性免疫系统，维持慢性炎症。该模型是抑制 IL-17A 信号作为一种潜在的治疗方法来破坏银屑病炎症循环的基础。几种抑制 IL-17 途径的单克隆抗体正在临床开发中。这些药物具有良好的临床疗效和耐受性特征，包括银屑病斑块的免疫组织化学改善。IL-17 途径抑制剂临床试验的结果正在深化我们对银屑病发病机制的理解，并可能为中重度银屑病患者提供新的治疗方法。
