Zhao Huai-Bo, Zhang Ya-Nan, Qiang Yan, Wang Guo-Mi, Wang Li-Wei, Jiang Wen-Cheng, Chen Xi
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Eight Departments of Traditional Chinese Medicine Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Immunol. 2025 Sep 1;16:1621492. doi: 10.3389/fimmu.2025.1621492. eCollection 2025.
Alopecia areata (AA) is a prevalent autoimmune condition characterized by hair loss, with the collapse of hair follicle immune privilege being a pivotal event in its pathogenesis. This collapse involves intricate immunological disturbances, where CD8NKG2D T cells, driven by inflammatory cytokines like IFN-γ, attack hair follicles. Additionally, various immune cell, including Th1, Th2, Th17 cells, γδT cells, NK cells, and mast cells, contribute to this pathological process. Defects in the function of Tregs, Bregs, and iNKT cells further compound the immune imbalance. At the molecular level, the JAK-STAT pathway emerges as a central regulatory node integrating multiple cytokine signals and presenting itself as a significant therapeutic target. JAK inhibitors have shown notable effectiveness in clinical settings, with some agents even gaining FDA approval for treating moderate-to-severe AA. However, the effectiveness of targeting IL-17, TNF-α, Th2 cytokines, PDE4, and other molecules remains debated. This review comprehensively explores the dynamic interactions among immune cell subsets, cytokine networks, and crucial signaling pathways in AA pathogenesis. It also summarizes the latest clinical progress and challenges in targeted therapies. Future studies should delve deeper into AA's immune regulatory framework and devise tailored treatment approaches to enhance patient outcomes.
斑秃（AA）是一种常见的自身免疫性疾病，其特征为脱发，毛囊免疫豁免的崩溃是其发病机制中的关键事件。这种崩溃涉及复杂的免疫紊乱，其中由IFN-γ等炎性细胞因子驱动的CD8⁺NKG2D⁺ T细胞会攻击毛囊。此外，包括Th1、Th2、Th17细胞、γδT细胞、NK细胞和肥大细胞在内的各种免疫细胞也参与了这一病理过程。调节性T细胞（Tregs）、调节性B细胞（Bregs）和不变自然杀伤T细胞（iNKT细胞）的功能缺陷进一步加剧了免疫失衡。在分子水平上，JAK-STAT信号通路是整合多种细胞因子信号的核心调节节点，也是一个重要的治疗靶点。JAK抑制剂在临床环境中已显示出显著疗效，一些药物甚至已获得美国食品药品监督管理局（FDA）批准用于治疗中度至重度斑秃。然而，针对白细胞介素-17（IL-17）、肿瘤坏死因子-α（TNF-α）、Th2细胞因子、磷酸二酯酶4（PDE4）和其他分子的治疗效果仍存在争议。本综述全面探讨了斑秃发病机制中免疫细胞亚群、细胞因子网络和关键信号通路之间的动态相互作用。它还总结了靶向治疗的最新临床进展和挑战。未来的研究应更深入地探究斑秃的免疫调节框架，并设计出量身定制的治疗方法以改善患者预后。
