CCL13在慢性鼻窦炎与哮喘中的作用及转化价值

Role and Translational Value of CCL13 in Chronic Rhinosinusitis and Asthma

摘要:

慢性鼻窦炎（CRS）与哮喘均为异质性较高的慢性气道炎症性疾病，可呈2型或非2型炎症内型；其中2型炎症在慢性鼻窦炎伴鼻息肉（CRSwNP）及部分哮喘表型中较为突出。C-C基序趋化因子配体13（CCL13），又名单核细胞趋化蛋白-4，可通过CC趋化因子受体2（CCR2）、CC趋化因子受体3（CCR3）等受体参与嗜酸性粒细胞、嗜碱性粒细胞、2型辅助性T细胞及单核-巨噬细胞的迁移和活化，在炎症放大及组织重塑中发挥作用。现有研究表明，CCL13在CRS（尤其是嗜酸性炎症占优势的CRSwNP）鼻黏膜组织中显著升高，并与术后复发风险、糖皮质激素治疗反应及白细胞介素13通路抑制的药效变化相关；在哮喘中，CCL13在血浆及支气管肺泡灌洗液中升高并与急性加重相关。然而，表达升高并不等同于致病因果，其作为生物标志物、致病介质和治疗靶点的证据强度并不一致。本文基于“来源-受体-效应-临床终点”证据链，系统评估CCL13在CRS中的转化定位，并结合哮喘证据进行对照分析。当前证据支持CCL13作为2型炎症相关候选生物标志物及药效动力学指标具有较高潜力，但作为独立治疗靶点仍缺乏充分依据。未来需通过同一患者上下气道配对研究及人源功能模型，明确其因果作用及临床增量价值，为精准分型及个体化治疗提供依据。

Abstract:

Chronic rhinosinusitis (CRS) and asthma are highly heterogeneous chronic inflammatory airway diseases that may exhibit either type 2 or non-type 2 inflammatory endotypes. Type 2 inflammation is particularly prominent in chronic rhinosinusitis with nasal polyps (CRSwNP) and in certain asthma phenotypes. C-C motif chemokine ligand 13 (CCL13), also known as monocyte chemoattractant protein-4, participates in the migration and activation of eosinophils, basophils, type 2 helper T cells, and monocyte-macrophage lineages through receptors such as C-C chemokine receptor 2 (CCR2) and C-C chemokine receptor 3 (CCR3), thereby playing important roles in inflammatory amplification and tissue remodeling. Current evidence indicates that CCL13 is significantly upregulated in the nasal mucosa of patients with CRS, particularly in CRSwNP characterized by eosinophilic inflammation, and is associated with the risk of postoperative recurrence, response to glucocorticoid therapy, and pharmacodynamic changes following inhibition of the interleukin-13 pathway. In asthma, elevated CCL13 levels have been detected in plasma and bronchoalveolar lavage fluid and have been associated with acute exacerbations. However, increased expression does not necessarily indicate a causal role in disease pathogenesis, and the strength of evidence supporting CCL13 as a biomarker, pathogenic mediator, or therapeutic target remains inconsistent. Based on a “source–receptor–effect–clinical endpoint” evidence framework, this review systematically evaluates the translational positioning of CCL13 in CRS and provides a comparative analysis incorporating evidence from asthma. Current evidence suggests that CCL13 has considerable potential as a candidate biomarker of type 2 inflammation and as a pharmacodynamic indicator; however, evidence supporting its use as an independent therapeutic target remains insufficient. Future studies should employ paired upper- and lower-airway investigations in the same patients and human-derived functional models to clarify its causal role and incremental clinical value, thereby providing a basis for precision endotyping and individualized treatment.