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

## TL;DR

This study shows that a specific type of neutrophil is more common in osteoarthritic tissue and can activate T cells, suggesting a new role for these immune cells in joint disease.

## Contribution

The discovery of HLA-DR+ neutrophils in osteoarthritic infrapatellar fat pad and their antigen-presenting function is novel.

## Key findings

- HLA-DR+ neutrophils in OA infrapatellar fat pad stimulate T cell proliferation.
- OA infrapatellar fat pad shows increased fibrosis and immune cell persistence.
- HLA-DR+ neutrophils have a distinct proteomic profile linked to metabolic and anti-apoptotic activity.

## Abstract

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.

•OA IFP is more fibrotic with immune cell persistence•Neutrophils are enriched in OA IFP compared to preOA IFP•OA IFP neutrophils have an antigen-presenting HLADR+ CD74+ phenotype•HLADR+ neutrophils from OA IFP stimulate T cell proliferation in vitro

OA IFP is more fibrotic with immune cell persistence

Neutrophils are enriched in OA IFP compared to preOA IFP

OA IFP neutrophils have an antigen-presenting HLADR+ CD74+ phenotype

HLADR+ neutrophils from OA IFP stimulate T cell proliferation in vitro

Immunology; Proteomics