Low-density neutrophil subsets in allergic rhinitis: heterogeneity and an emerging hypothesis for the non-type 2 endotype

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.