Van Caelenberg Elise, Belpaire Arno, van Geel Nanja, Speeckaert Reinhart
Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Dermatology, Ghent University Hospital, Ghent, Belgium.
Front Immunol. 2025 Sep 3;16:1648868. doi: 10.3389/fimmu.2025.1648868. eCollection 2025.
A deeper understanding of the immune-based pathogenesis of alopecia areata is essential for the development of novel targeted therapies. Compared to cytokines, chemokines exhibit substantially higher serum concentrations, offering a more robust approach for large-scale immune profiling. However, the complexity of chemokine interactions presents challenges in defining their precise roles in AA. To explore these dynamics, we conducted a scoping review and meta-analysis of 46 original research articles examining chemokine expression in skin and blood samples from AA patients; meta-analysis was performed when three or more studies assessed the same chemokine in comparable groups. Th1-associated chemokines-including CXCL9, CXCL10, CCL5, and CXCL11-were consistently elevated in AA, reflecting the known IFN-γ-driven response. A distinct Th2 chemokine signature was also observed, with increased levels of CCL13, CCL17, CCL22, and CX3CL1. Additionally, elevated levels of CCL2, CCL3, CCL4 (monocyte/dendritic cell recruitment), and CCL11, CCL24, and CCL26 (eosinophil recruitment) suggest the involvement of immune pathways beyond classical T helper subsets. Meta-analysis confirmed significantly elevated serum levels of CXCL9 (p = 0.003), CXCL10 (p = 0.004), CXCL8 (p < 0.001), and CCL17 (p < 0.001). These findings reveal a complex chemokine profile in AA, dominated by Th1 activity but also implicating Th2 and other immune pathways, highlighting the potential benefit of broader immunomodulatory strategies to address the multifaceted immune dysregulation underlying the disease.
深入了解斑秃基于免疫的发病机制对于开发新型靶向疗法至关重要。与细胞因子相比，趋化因子在血清中的浓度显著更高，为大规模免疫分析提供了一种更有效的方法。然而，趋化因子相互作用的复杂性给确定它们在斑秃中的精确作用带来了挑战。为了探究这些动态变化，我们对46篇原始研究文章进行了范围综述和荟萃分析，这些文章研究了斑秃患者皮肤和血液样本中的趋化因子表达；当三项或更多研究在可比组中评估相同趋化因子时进行荟萃分析。与Th1相关的趋化因子，包括CXCL9、CXCL10、CCL5和CXCL11，在斑秃中持续升高，反映了已知的IFN-γ驱动的反应。还观察到了独特的Th2趋化因子特征，CCL13、CCL17、CCL22和CX3CL1的水平升高。此外，CCL2、CCL3、CCL4（单核细胞/树突状细胞募集）以及CCLll、CCL24和CCL26（嗜酸性粒细胞募集）水平升高表明除了经典的T辅助亚群之外，免疫途径也参与其中。荟萃分析证实血清中CXCL9（p = 0.003）、CXCL10（p = 0.004）、CXCL8（p < 0.001）和CCL17（p < 0.001）水平显著升高。这些发现揭示了斑秃中复杂的趋化因子谱，以Th1活性为主，但也涉及Th2和其他免疫途径，突出了更广泛的免疫调节策略在解决该疾病潜在的多方面免疫失调方面的潜在益处。
