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Zweig Memorial Fund for Equine Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010282","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["beva.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Equine Veterinary Journal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There is emerging evidence for the role of the immune system in osteoarthritis (OA) pathophysiology; however, little is known about how immune cells and the synovial transcriptome are altered in naturally occurring equine OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate synovial fluid (SF) and synovial membrane (SM) immune cell populations and the SM transcriptome in racehorses with fetlock OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Cross\u2010sectional cadaver study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fetlock joints from racehorses euthanised at NY racetracks were considered for inclusion. SF and SM were analysed by flow cytometry using T\u2010cell (CD3, CD4, CD8) and macrophage (CD14, CD86, CD206) surface markers. OA severity was characterised by gross joint evaluation and SM histology. Bulk RNA\u2010sequencing of SM was performed to identify differentially expressed genes. Flow cytometry data were analysed with mixed linear modelling, including OA severity as a fixed effect and horse as a random effect. RNA\u2010sequencing data were evaluated with mixed linear and quadratic modelling using DREAMSeq method to capture differential gene expression over the range of OA severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010four fetlocks from 12 horses met inclusion criteria. CD8+ T\u2010cells (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.25 for SM, 0.35 for SF) and CD86+ macrophages (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.14 for SM) were positively correlated with OA severity, while CD4+ T\u2010cells (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.17 for SM, 0.31 for SF) were negatively correlated. Macrophages co\u2010expressing CD86 and CD206 correlated with OA severity in SM (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.31). Pathways including those associated with TNF\u2010\u03b1 signalling, connective tissue development and cell and neuron projection organisation\/development were differentially regulated in SM with greater OA scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Limitations<\/jats:title>\n                    <jats:p>Limited sample size, particularly of horses with severe OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CD8+ T\u2010cells, CD86+ macrophages and macrophages co\u2010expressing CD206 and CD86 are enriched in horses with more advanced OA. Gene set analysis suggests the importance of TNF\u2010\u03b1 signalling and disinhibition of neuron and cell projection development in OA pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/evj.70168","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:04:33Z","timestamp":1777525473000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CD8<\/scp>\n                    + T\u2010cells,\n                    <scp>CD86<\/scp>\n                    + macrophages and\n                    <scp>TNF<\/scp>\n                    \u2010\u03b1 signalling pathways are correlated with fetlock osteoarthritis in racehorses"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-5444","authenticated-orcid":false,"given":"E. 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