银屑病核心免疫炎症机制和关键调控靶点综述

摘要(中文译文)

银屑病是一种慢性免疫介导的炎症性皮肤病，由固有免疫细胞与适应性免疫细胞之间失调的相互作用所致。值得注意的是，IL-23/Th17轴是已知通路中新的核心环路，而TNF-α、IL-17家族细胞因子和IL-36介导角质形成细胞功能障碍及组织炎症。一个相互连接的炎症网络涉及树突状细胞、T细胞群体、角质形成细胞、中性粒细胞和成纤维细胞，该网络促进表皮过度增殖及病灶处免疫细胞募集。靶向TNF-α、IL-17和IL-23的生物制剂在疾病治疗中具有变革性临床意义，但仍有大量患者存在应答不完全、耐药或长期管理困难的问题。其他新靶点如IL-36R和AHR可能拓展治疗机会的窗口。分子分层和生物标志物驱动的治疗选择也值得在进一步明确特定治疗策略的同时开展研究。

Abstract

Psoriasis is a chronic immune-mediated inflammatory skin disease caused by dysregulated interaction between innate and adaptive immune cells. Of note, the IL-23/Th17 axiom is new central circuit amongst known pathways, while TNF-alpha, IL-17 family cytokines and IL-36 mediate the dysfunction of keratinocyte and tissue in inflammation. An interconnecting inflammatory network involves dendritic cells, T-cell populations, keratinocytes, neutrophils and fibroblasts that plate epidermal hyperproliferation and lesional immune-cell recruitment. Biologics targeting TNF-alpha and IL-17 and IL-23 are clinically transformative in the treatment of disease, but a large cohort of patients are left with incomplete response, resistance or challenges in long-term management. Other novel targets such IL-36R and AHR may extend the window of therapeutic opportunity. Molecular stratification and biomarker-driven treatment selection also merit investigation in parallel with further delineation of a specific therapeutic strategy.

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