Context-Dependent Roles of Siglec-F⁺ Neutrophils

Recent studies in murine disease models have identified Siglec-F⁺ neutrophils, which express a marker traditionally associated with eosinophils, as a functionally distinct population characterized by extended lifespans and context-dependent roles. While conventional neutrophils typically return to the bone marrow or undergo apoptosis at the site of inflammation, these cells remain in tissues for extended periods. These cells demonstrate remarkable functional plasticity, promote bacterial clearance and immune activation during infections, foster immunosuppression and tumor progression in cancer, and contribute to tissue remodeling in fibrotic diseases. In this review, we examine the key features governing Siglec-F⁺ neutrophil differentiation and function-including Siglec-F signaling, metabolic programming, and upstream cytokine cues-and explore how targeting these pathways may offer promising avenues for precision immunomodulation.