Increased circulating LOX-1⁺ neutrophils activate T cells and demonstrate a pro-inflammatory role in allergic...

Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear.

In the present study, we defined low-density neutrophils as CD14^-CD11B⁺CD15⁺LOX-1⁺ (LOX-1⁺ neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3⁺ T cells were cultured alone or with LOX-1⁺ neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1⁺ neutrophils.

We determined that LOX-1⁺ neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1⁺ neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1⁺ neutrophil levels and the levels of IgE, age and sex.

These findings indicate that elevated circulating LOX-1⁺ neutrophils play a pro-inflammatory role in AR.