Neutrophil Fate and Function in Gout: From Sterile Inflammation to Resolution.

Gout is a prototypical sterile inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Although acute gout flares are characterized by rapid and intense neutrophil-dominated inflammation, they often resolve spontaneously, suggesting that neutrophils may contribute not only to inflammatory amplification but also to endogenous resolution. In this review, we summarize current evidence on the multifaceted roles of neutrophils in gout across different stages of disease. We discuss how MSU crystals activate innate immune signaling and promote neutrophil recruitment, activation, and effector responses, thereby driving acute inflammation. We further examine the diverse neutrophil programs involved in gout, including apoptosis, necroptosis, pyroptosis, autophagy, efferocytosis, and NET release. Particular attention is given to the dual roles of NETs in gout, as they can both amplify inflammation and, in their aggregated form, facilitate cytokine degradation, crystal sequestration, and inflammation resolution. In addition, we address the potential contribution of neutrophil-derived extracellular vesicles and neutrophil-associated mechanisms to tophus formation and chronic disease progression. By integrating recent advances and ongoing controversies, this review highlights neutrophils as dynamic regulators of both inflammatory injury and resolution in gout, and underscores their potential as therapeutic targets in immune-mediated crystal inflammation.