{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:05:42Z","timestamp":1790888742873,"version":"4.1.0"},"reference-count":142,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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>Osteoarthritis (OA) is a disorder of the whole-joint microenvironment involving mechanical loading, aging, metabolic stress, and dysregulated immune homeostasis. Within the OA joint microenvironment, senescent chondrocytes, synovial fibroblasts, and diverse immune cell populations contribute to a persistently amplified inflammatory network through the senescence-associated secretory phenotype (SASP), damage-associated molecular patterns (DAMPs), and signaling pathways mediated by metabolic reprogramming. In this context, inflammaging and immunosenescence are considered key mechanistic axes linking aging, chronic low-grade inflammation, cartilage matrix degradation, synovial inflammation, and subchondral bone remodeling, thereby playing central roles in OA pathogenesis. As a narrative review, this article aims to provide an integrated analysis of the cellular basis, molecular mechanisms, joint immune microenvironment, biomarkers, and immune reprogramming strategies related to inflammaging and immunosenescence in OA. Particular emphasis is placed on macrophage polarization, senescent cell clearance, SASP inhibition, and gene-editing approaches. This review highlights that future OA treatment may gradually shift from symptom-oriented management toward disease-modifying therapy based on the identification of immune endotypes. Nevertheless, further studies are required to validate the underlying molecular mechanisms, evaluate safety, and conduct clinical trials, thereby facilitating the clinical translation of immune reprogramming strategies for OA.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1892251","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:28:37Z","timestamp":1787056117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammaging and immunosenescence-driven remodeling of the immune microenvironment in osteoarthritis: mechanisms, immune regulation and immune reprogramming"],"prefix":"10.3389","volume":"17","author":[{"given":"Tong","family":"Wang","sequence":"first","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute, Ministry of Education (MOE) Key Lab for Neuroinformation, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Affiliated Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Suining Central Hospital","place":["Suining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Suining Central Hospital","place":["Suining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Suining Central Hospital","place":["Suining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Suining Central Hospital","place":["Suining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3390\/antibiotics14060609","article-title":"Is osteoarthritis a state of joint dysbiosis","volume":"14","author":"He","year":"2025","journal-title":"Antibiotics (Basel)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1142\/s0192415x2550003x","article-title":"Gut microbiota and osteoarthritis: From pathogenesis to novel therapeutic opportunities","volume":"53","author":"Yujiang","year":"2025","journal-title":"Am J Chin Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/nu17020264","article-title":"Relationship between the gut microbiome, tryptophan-derived metabolites, and osteoarthritis-related pain: a systematic review with meta-analysis","volume":"17","author":"Erika","year":"2025","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. 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