The regulatory effects of hypoxic environment on neutrophil function and the related molecular mechanisms

Metabolic remodeling is involved in multiple diseases, including tumors, acute and chronic inflammations, but our understanding of the molecular pathways remains limited. Neutrophils, as pivotal effector cells of the innate immune system, exhibit significant functional heterogeneity influenced by the hypoxic microenvironment, a prevalent pathological feature of diseases. Emerging evidence reveals that disease progression is tightly linked to this regulatory mechanism. This review focuses on the functional remodeling of neutrophils under hypoxic stress, systematically elucidates the mechanisms by which neutrophils monitor and respond to hypoxia, the metabolic and functional changes that occur in neutrophils under hypoxic conditions, and the impact of these changes on the progression of associated diseases. Furthermore, it provides several potential intervention targets and may offer insights for the treatment of disorders with hypoxic microenvironments.