Enrichment of HLA-DR⁺ neutrophils in osteoarthritic infrapatellar fat pad

Neutrophils are increasingly recognized as functionally versatile immune cells, with tissue-specific phenotypes that extend beyond their classical role in acute inflammation. In osteoarthritis (OA), neutrophils are abundant in synovial fluid (SF), which has been linked to worse symptoms. Here, we characterized neutrophils in OA IFP and identified a distinct population of HLA-DR⁺ neutrophils enriched in OA IFP. Sorted IFP HLA-DR⁺ neutrophils induced the proliferation of autologous CD3⁺ T cells, supporting their role in antigen presentation. Proteomic profiling of OA IFP revealed the upregulation of metabolic and enzymatic activities as well as the downregulation of apoptotic and enzyme inhibition pathways, consistent with the increased fibrosis and neovascularization observed histologically. Collectively, our findings expand the functional scope of neutrophils in arthritic diseases, further establishing their potential in antigen presentation, and position the IFP as a previously underappreciated, immunologically active niche in OA pathogenesis.