{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:26:30Z","timestamp":1787066790088,"version":"build-2736575974"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Osteoarthritis (OA) is increasingly recognized as an immune-associated whole-joint disorder characterized by chronic low-grade inflammation, which contributes to joint degeneration, structural deterioration, and persistent pain. Innate and adaptive immune cells, including macrophages, T cells, neutrophils, and mast cells, participate in OA pathogenesis by releasing pro-inflammatory cytokines, reactive oxygen species, and matrix-degrading enzymes, as well as by interacting with chondrocytes, synovial fibroblasts, and subchondral bone cells. Natural products, because of their multi-target pharmacological properties, have emerged as potential modulators of this complex immune microenvironment. This review critically appraises current evidence on natural-product interventions modulating OA-associated immune-cell responses, with particular emphasis on mechanistic evidence, evidence maturity, and translational potential. It further compares evidence across immune-cell populations to identify shared mechanisms, population-specific differences, and key translational gaps. Macrophage- and T-cell-associated responses have the most developed evidence base, with relatively consistent evidence supporting modulation of M1-like\/M2-like macrophage phenotypes and the T helper 17 (Th17)\/regulatory T (Treg) cell balance. Neutrophil- and mast-cell-associated responses represent emerging or auxiliary areas of evidence, as these immune-cell populations may amplify inflammation and pain through reactive oxygen species production, neutrophil extracellular trap formation, degranulation, and inflammatory mediator release. Evidence for B cells, dendritic cells (DCs), and natural killer (NK) cells remains limited; therefore, these immune-cell populations should currently be regarded as potential research directions rather than established therapeutic targets. Most available data derive from\n                    <jats:italic>in vitro<\/jats:italic>\n                    and animal studies, whereas clinical evidence is largely restricted to peripheral immune-marker changes and short-term symptom improvement. Future studies should integrate local joint immune profiling, functional validation, and stratified clinical designs to clarify the translational potential of natural products in OA immunomodulation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1883774","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:51:52Z","timestamp":1783698712000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Natural products and immune-cell responses in osteoarthritis: mechanisms, evidence maturity, and translational gaps"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinhu","family":"Jia","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, China"]},{"name":"Department of Rheumatology and Immunology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, 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