变应性鼻炎中的低密度中性粒细胞亚群：异质性及非2型内型的新兴假说

文献信息

中文摘要

背景： 变应性鼻炎（AR）传统上以2型/嗜酸性粒细胞为中心来审视，但相当一部分患者表现出以中性粒细胞为主、对糖皮质激素难治的炎症表型，对标准治疗反应不佳。中性粒细胞曾被视为均一的终末分化谱系，如今已被认识到是功能异质的群体。在其亚群中，低密度中性粒细胞（LDNs）——包括促炎性低密度粒细胞和免疫抑制性多形核髓源性抑制细胞——已成为固有免疫和适应性免疫的关键调节者。本小型综述综合现有证据，并提出一个新出现的假说：LDN异质性可能促成而非定义AR的非2型内型。我们讨论（i）LDNs的鉴定及其双重功能；（ii）AR特异性发现，包括以CD16/CD62L定义的中性粒细胞亚群以及近期描述的激活T细胞的循环LOX-1+中性粒细胞；（iii）可能放大非2型炎症的中性粒细胞-T细胞交互作用；（iv）LDNs作为生物标志物和治疗靶点的转化潜力。对LDN亚群更精确的表征可能有助于在AR中实现内型导向、针对中性粒细胞的治疗。

英文摘要

Allergic rhinitis (AR) is conventionally viewed through a type 2/eosinophil-centric lens, yet a substantial subgroup of patients exhibits a neutrophil-predominant, corticosteroid-refractory inflammatory phenotype that responds poorly to standard therapy. Once regarded as a homogeneous, terminally differentiated lineage, neutrophils are now recognized as a functionally heterogeneous population. Among their subsets, low-density neutrophils (LDNs)-encompassing pro-inflammatory low-density granulocytes and immunosuppressive polymorphonuclear myeloid-derived suppressor cells-have emerged as key regulators of innate and adaptive immunity. This Mini Review synthesizes current evidence and proposes an emerging hypothesis that LDN heterogeneity may contribute to, rather than define, the non-type 2 endotype of AR. We discuss (i) the identification and dual functionality of LDNs; (ii) AR-specific findings, including CD16/CD62L-defined neutrophil subsets and recently described circulating LOX-1 + neutrophils that activate T cells; (iii) the neutrophil-T cell crosstalk that may amplify non-type 2 inflammation; and (iv) the translational potential of LDNs as biomarkers and therapeutic targets. A tighter characterization of LDN subsets may enable endotype-guided, neutrophil-directed therapy in AR.