{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:20:23Z","timestamp":1793215223192,"version":"4.5.0"},"reference-count":169,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003452","name":"Innovation and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.phrs.2025.108041","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T14:08:35Z","timestamp":1763647715000},"page":"108041","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Adaptive immunity in osteoarthritis: Mechanisms and opportunities for regulatory T-cell\u2013targeted therapy"],"prefix":"10.1016","volume":"222","author":[{"given":"Xueyou","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingde","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruma Sai-Chuen","family":"FU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Quan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Tim-Yun","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Shu-Hang","family":"Yung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10264","key":"10.1016\/j.phrs.2025.108041_bib1","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(20)32230-3","article-title":"Osteoarthritis in 2020 and beyond: a Lancet Commission","volume":"396","author":"Hunter","year":"2020","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib2","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1186\/s12891-023-06663-9","article-title":"Post-traumatic osteoarthritis: the worst associated injuries and differences in patients' profile when compared with primary osteoarthritis","volume":"24","author":"Maia","year":"2023","journal-title":"BMC Musculoskelet. Disord."},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib3","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4085\/1062-6050-51.5.08","article-title":"Epidemiology of Posttraumatic Osteoarthritis","volume":"52","author":"Thomas","year":"2017","journal-title":"J. Athl. Train."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib4","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1177\/0363546507307396","article-title":"The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis","volume":"35","author":"Lohmander","year":"2007","journal-title":"Am. J. Sports Med."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib5","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41584-024-01102-y","article-title":"Molecular biomarker approaches to prevention of post-traumatic osteoarthritis","volume":"20","author":"Kraus","year":"2024","journal-title":"Nat. Rev. Rheuma"},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib6","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrrheum.2016.136","article-title":"Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis","volume":"12","author":"Robinson","year":"2016","journal-title":"Nat. Rev. Rheuma"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3899\/jrheum.140382","article-title":"The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive","volume":"42","author":"Orlowsky","year":"2015","journal-title":"J. Rheuma"},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib8","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Sanchez-Lopez","year":"2022","journal-title":"Nat. Rev. Rheuma"},{"issue":"11","key":"10.1016\/j.phrs.2025.108041_bib9","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.joca.2015.08.015","article-title":"Inflammation in joint injury and post-traumatic osteoarthritis","volume":"23","author":"Lieberthal","year":"2015","journal-title":"Osteoarthr. Cartil."},{"issue":"11","key":"10.1016\/j.phrs.2025.108041_bib10","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1038\/s12276-021-00710-y","article-title":"Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions","volume":"53","author":"Cho","year":"2021","journal-title":"Exp. Mol. Med"},{"key":"10.1016\/j.phrs.2025.108041_bib11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00441-016-2563-y","article-title":"Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice","volume":"368","author":"Hoshi","year":"2017","journal-title":"Cell Tissue Res."},{"issue":"6571","key":"10.1016\/j.phrs.2025.108041_bib12","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1126\/science.abi5200","article-title":"The spectrum of inflammatory responses","volume":"374","author":"Medzhitov","year":"2021","journal-title":"Science"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.joca.2021.12.007","article-title":"Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing","volume":"30","author":"Huang","year":"2022","journal-title":"Osteoarthr. Cartil."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-67730-y","article-title":"Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis","volume":"10","author":"Chou","year":"2020","journal-title":"Sci. Rep."},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41584-025-01223-y","article-title":"The role of the immune system in osteoarthritis: mechanisms, challenges and future directions","volume":"21","author":"Moulin","year":"2025","journal-title":"Nat. Rev. Rheuma"},{"key":"10.1016\/j.phrs.2025.108041_bib16","series-title":"Arthritis and Rheumatism","article-title":"Oligoclonal populations of T-cells infiltrate the synovial membrane (SM) of patients with osteoarthritis (OA)","author":"Scanzello","year":"1999"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib17","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1053\/joca.1998.0224","article-title":"T-cell mediated inflammatory pathway in osteoarthritis","volume":"7","author":"Nakamura","year":"1999","journal-title":"Osteoarthr. Cartil."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib18","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1172\/JCI115866","article-title":"Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium","volume":"90","author":"Williams","year":"1992","journal-title":"J. Clin. Investig."},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib19","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1089\/dna.1994.13.923","article-title":"V alpha gene usage in rheumatoid compared with osteoarthritic synovial tissue T cells","volume":"13","author":"ZWILLICH","year":"1994","journal-title":"DNA Cell Biol."},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib20","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1073\/pnas.85.4.1179","article-title":"Clonal dominance among T-lymphocyte infiltrates in arthritis","volume":"85","author":"Stamenkovic","year":"1988","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.phrs.2025.108041_bib21","article-title":"Mechanical loading of joint modulates T cells in lymph nodes to regulate osteoarthritis","author":"Wheeler","year":"2023","journal-title":"Osteoarthr. Cartil."},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib22","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.joca.2011.02.014","article-title":"T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1\u03b3","volume":"19","author":"Shen","year":"2011","journal-title":"Osteoarthr. Cartil."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib23","doi-asserted-by":"crossref","first-page":"19951","DOI":"10.3390\/ijms141019951","article-title":"CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis","volume":"14","author":"Hsieh","year":"2013","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib24","doi-asserted-by":"crossref","first-page":"557","DOI":"10.4049\/jimmunol.178.1.557","article-title":"B cell clonal expansion and somatic hypermutation of Ig variable heavy chain genes in the synovial membrane of patients with osteoarthritis","volume":"178","author":"Da","year":"2007","journal-title":"J. Immunol."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib25","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1136\/ard.60.8.802","article-title":"Clonal analysis of B cells in the osteoarthritis synovium","volume":"60","author":"Shiokawa","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.phrs.2025.108041_bib26","article-title":"The Immunological Facets Of Chondrocytes In Osteoarthritis: A Narrative Review","author":"Sengprasert","year":"2023","journal-title":"J. Rheuma"},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib27","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.joca.2023.03.017","article-title":"B-cell capacity for expansion and differentiation into plasma cells are altered in osteoarthritis","volume":"31","author":"Xie","year":"2023","journal-title":"Osteoarthr. Cartil."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/ar643","article-title":"Autoantibodies in osteoarthritis","volume":"5","author":"Menard","year":"2003","journal-title":"Arthritis Res Ther."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/art.22369","article-title":"The role of T cells in the pathogenesis of osteoarthritis","volume":"56","author":"Sakkas","year":"2007","journal-title":"Arthritis Rheum."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib30","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010758","article-title":"Osteoarthritis increases the risk of inflammatory arthritis due to immune checkpoint inhibitors associated with tissue-resident memory T cells","volume":"13","author":"Paiola","year":"2025","journal-title":"J. Immunother. Cancer"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/cei.13230","article-title":"A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood, synovial fluid and synovial membrane","volume":"195","author":"Rosshirt","year":"2019","journal-title":"Clin. Exp. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib32","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2023.01.004","article-title":"Principles of regulatory T cell function","volume":"56","author":"Dikiy","year":"2023","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13075-020-02410-w","article-title":"Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis","volume":"23","author":"Rosshirt","year":"2021","journal-title":"Arthritis Res Ther."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib34","doi-asserted-by":"crossref","DOI":"10.1186\/ar4545","article-title":"CD4\u207aCD25\u207a\/highCD127low\/\u207b regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints--analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood","volume":"16","author":"Moradi","year":"2014","journal-title":"Arthritis Res Ther."},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib35","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10092111","article-title":"Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability","volume":"10","author":"Nees","year":"2022","journal-title":"Biomedicines"},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13075-017-1305-1","article-title":"Differences in serum and synovial CD4+ T cells and cytokine profiles to stratify patients with inflammatory osteoarthritis and rheumatoid arthritis","volume":"19","author":"Penatti","year":"2017","journal-title":"Arthritis Res Ther."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib37","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13075-023-03110-x","article-title":"Cellular characterisation of advanced osteoarthritis knee synovium","volume":"25","author":"Mimpen","year":"2023","journal-title":"Arthritis Res. Ther."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib38","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","article-title":"Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review","volume":"20","author":"de Lange-Brokaar","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.phrs.2025.108041_bib39","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s10067-008-0878-0","article-title":"A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans\u2019 Illness and joint pain compared to normal and osteoarthritis synovium","volume":"27","author":"Pessler","year":"2008","journal-title":"Clin. Rheumatol."},{"key":"10.1016\/j.phrs.2025.108041_bib40","article-title":"Targeting YAP1-regulated glycolysis in fibroblast-like synoviocytes impairs macrophage infiltration to ameliorate diabetic osteoarthritis progression","author":"Yang","year":"2023","journal-title":"Adv. Sci."},{"key":"10.1016\/j.phrs.2025.108041_bib41","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.93283","article-title":"Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis","volume":"12","author":"Knights","year":"2025","journal-title":"Elife"},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/annrheumdis-2017-212863","article-title":"Single-cell RNA-seq analysis reveals the progression of human osteoarthritis","volume":"78","author":"Ji","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.phrs.2025.108041_bib43","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF00541597","article-title":"The tissue architecture of synovial membranes in inflammatory and non-inflammatory joint diseases: I. The localization of the major synovial cell populations as detected by monoclonal reagents directed towards Ia and monocyte-macrophage antigens","volume":"3","author":"Burmester","year":"1983","journal-title":"Rheumatol. Int."},{"key":"10.1016\/j.phrs.2025.108041_bib44","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/00003086-199306000-00032","article-title":"The expression of major histocompatibility antigens on human articular chondrocytes","volume":"291","author":"LANCE","year":"1993","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib45","first-page":"704","article-title":"Osteoarthritic articular chondrocytes stimulate autologous T cell responses in vitro","volume":"21","author":"Sakata","year":"2003","journal-title":"Clin. Exp. Rheumatol."},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib46","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1136\/ard.47.4.300","article-title":"The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies","volume":"47","author":"Revell","year":"1988","journal-title":"Ann. Rheum. Dis."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib47","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/art.1780301001","article-title":"Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis","volume":"30","author":"Lindblad","year":"1987","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"10.1016\/j.phrs.2025.108041_bib48","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00296-008-0518-7","article-title":"Early lymphocyte activation in the synovial microenvironment in patients with osteoarthritis: comparison with rheumatoid arthritis patients and healthy controls","volume":"28","author":"Rollin","year":"2008","journal-title":"Rheumatol. Int."},{"issue":"7","key":"10.1016\/j.phrs.2025.108041_bib49","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat. Immunol."},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib50","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1053\/joca.2001.0509","article-title":"Characterization of infiltrating T cells and Th1\/Th2-type cytokines in the synovium of patients with osteoarthritis","volume":"10","author":"Ishii","year":"2002","journal-title":"Osteoarthr. Cartil."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib51","first-page":"315","article-title":"Immunophenotyping of synovial tissue in adolescents undergoing acl reconstruction: what is the role of synovial inflammation in arthrofibrosis?","volume":"53","author":"Romereim","year":"2025","journal-title":"Am. J. Sports Med"},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib52","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1002\/jor.24899","article-title":"Degenerative joint changes following intra-articular fracture are more severe in mice with T cell deficiency","volume":"39","author":"Buchanan","year":"2021","journal-title":"J. Orthop. Res"},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib53","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1136\/ard.60.8.802","article-title":"Clonal analysis of B cells in the osteoarthritis synovium","volume":"60","author":"Shiokawa","year":"2001","journal-title":"Ann. Rheum. Dis."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib54","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.joca.2023.10.009","article-title":"Comparative analysis of late-stage rheumatoid arthritis and osteoarthritis reveals shared histopathological features","volume":"32","author":"Boutet","year":"2024","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.phrs.2025.108041_bib55","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.39905","article-title":"IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis","volume":"8","author":"Wang","year":"2019","journal-title":"Elife"},{"issue":"7","key":"10.1016\/j.phrs.2025.108041_bib56","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.it.2013.03.005","article-title":"Adaptive immunity after cell death","volume":"34","author":"Zelenay","year":"2013","journal-title":"Trends Immunol."},{"key":"10.1016\/j.phrs.2025.108041_bib57","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.695257","article-title":"Mitochondria in Injury, Inflammation and Disease of Articular Skeletal Joints","volume":"12","author":"Early","year":"2021","journal-title":"Front Immunol."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/art.1780280302","article-title":"Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis","volume":"28","author":"Jasin","year":"1985","journal-title":"Arthritis Rheum."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib59","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/joca.2001.0494","article-title":"Increased cellular infiltrate in inflammatory synovia of osteoarthritic knees","volume":"10","author":"Saito","year":"2002","journal-title":"Osteoarthr. Cartil."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib60","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/art.1780300311","article-title":"Antibodies to canine collagen types I and II in dogs with spontaneous cruciate ligament rupture and osteoarthritis","volume":"30","author":"Niebauer","year":"1987","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"10.1016\/j.phrs.2025.108041_bib61","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00296-004-0497-2","article-title":"The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes","volume":"26","author":"Du","year":"2005","journal-title":"Rheumatol. Int."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib62","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1002\/art.1780391207","article-title":"Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases","volume":"39","author":"Karopoulos","year":"1996","journal-title":"Arthritis Rheum."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib63","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/art.20189","article-title":"Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphate isomerase as an autoantigen in patients with osteoarthritis","volume":"50","author":"Xiang","year":"2004","journal-title":"Arthritis Rheum."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib64","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/1529-0131(199904)42:3<527::AID-ANR18>3.0.CO;2-M","article-title":"Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis","volume":"42","author":"Guerassimov","year":"1999","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"issue":"01","key":"10.1016\/j.phrs.2025.108041_bib65","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1136\/ard.2008.103978","article-title":"Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis","volume":"69","author":"de Jong","year":"2010","journal-title":"Ann. Rheum. Dis."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib66","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1093\/rheumatology\/39.12.1326","article-title":"Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions","volume":"39","author":"Vos","year":"2000","journal-title":"Rheumatology"},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib67","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41577-023-00835-3","article-title":"Can we predict T cell specificity with digital biology and machine learning?","volume":"23","author":"Hudson","year":"2023","journal-title":"Nat. Rev. Immunol."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib68","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbae210","article-title":"Predicting TCR sequences for unseen antigen epitopes using structural and sequence features","volume":"25","author":"Ji","year":"2024","journal-title":"Brief. Bioinforma."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib69","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1016\/j.immuni.2022.11.009","article-title":"The pathogenesis of rheumatoid arthritis","volume":"55","author":"Alivernini","year":"2022","journal-title":"Immunity"},{"issue":"23","key":"10.1016\/j.phrs.2025.108041_bib70","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. Engl. J. Med"},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib71","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1136\/annrheumdis-2021-221761","article-title":"Distinct stromal and immune cell interactions shape the pathogenesis of rheumatoid and psoriatic arthritis","volume":"81","author":"Floudas","year":"2022","journal-title":"Ann. Rheum. Dis."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib72","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/art.20217","volume":"50","author":"Keystone","year":"2004","journal-title":"Arthritis Rheum."},{"issue":"9617","key":"10.1016\/j.phrs.2025.108041_bib73","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","article-title":"Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial","volume":"371","author":"Smolen","year":"2008","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib74","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1136\/annrheumdis-2015-207628","article-title":"Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial","volume":"75","author":"Burmester","year":"2016","journal-title":"Ann. Rheum. Dis."},{"issue":"7","key":"10.1016\/j.phrs.2025.108041_bib75","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"N. Engl. J. Med"},{"issue":"14","key":"10.1016\/j.phrs.2025.108041_bib76","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1056\/NEJMoa1412679","article-title":"Secukinumab Inhibition of Interleukin-17A in patients with psoriatic arthritis","volume":"373","author":"Mease","year":"2015","journal-title":"N. Engl. J. Med"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib77","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/art.42010","volume":"74","author":"McInnes","year":"2022","journal-title":"Arthritis Rheuma"},{"issue":"13","key":"10.1016\/j.phrs.2025.108041_bib78","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMoa2022516","article-title":"Trial of upadacitinib and adalimumab for psoriatic arthritis","volume":"384","author":"McInnes","year":"2021","journal-title":"N. Engl. J. Med"},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib79","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1002\/art.21249","article-title":"Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study","volume":"52","author":"Baslund","year":"2005","journal-title":"Arthritis Rheum."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib80","doi-asserted-by":"crossref","DOI":"10.1186\/ar3817","article-title":"Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features","volume":"14","author":"Celis","year":"2012","journal-title":"Arthritis Res Ther."},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076292","article-title":"Interleukin 15 primes natural killer cells to kill via NKG2D and cPLA2 and this pathway is active in psoriatic arthritis","volume":"8","author":"Tang","year":"2013","journal-title":"PLoS One"},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib82","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1172\/JCI200318986","article-title":"Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model","volume":"112","author":"Villadsen","year":"2003","journal-title":"J. Clin. Invest"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib83","doi-asserted-by":"crossref","DOI":"10.1016\/j.ocarto.2023.100404","article-title":"Efficacy of tumor necrosis factor inhibitors in hand osteoarthritis: a systematic review and meta-analysis of randomized controlled trials","volume":"5","author":"Estee","year":"2023","journal-title":"Osteoarthr. Cartil. Open"},{"key":"10.1016\/j.phrs.2025.108041_bib84","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/annrheumdis-2022-eular.3422","article-title":"OP0229 Osteoarthritis of the knee, inflammation, and the effect of adalimumab (OKINADA): A randomized placebo-controlled trial","volume":"81","author":"Maksymowych","year":"2022","journal-title":"Ann. Rheum. Dis."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib85","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1136\/annrheumdis-2020-218547","article-title":"Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial","volume":"80","author":"Richette","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.phrs.2025.108041_bib86","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3389\/fimmu.2020.01385","article-title":"IL-15 and IL15RA in Osteoarthritis: Association With Symptoms and Protease Production, but Not Structural Severity","volume":"11","author":"Warner","year":"2020","journal-title":"Front Immunol."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib87","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.joca.2009.02.011","article-title":"Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease","volume":"17","author":"Scanzello","year":"2009","journal-title":"Osteoarthr. Cartil."},{"issue":"7","key":"10.1016\/j.phrs.2025.108041_bib88","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1001\/jamainternmed.2025.1359","article-title":"Low-dose methotrexate for the treatment of inflammatory knee osteoarthritis: a randomized clinical trial","volume":"185","author":"Zhu","year":"2025","journal-title":"JAMA Intern Med"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib89","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ni1037","article-title":"Regulatory T cells mediate maternal tolerance to the fetus","volume":"5","author":"Aluvihare","year":"2004","journal-title":"Nat. Immunol."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib90","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ni.2001","article-title":"The immune system in atherosclerosis","volume":"12","author":"Hansson","year":"2011","journal-title":"Nat. Immunol."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib91","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nm.2002","article-title":"Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters","volume":"15","author":"Feuerer","year":"2009","journal-title":"Nat. Med"},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib92","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/ni.2683","article-title":"Regulatory T cells in nonlymphoid tissues","volume":"14","author":"Burzyn","year":"2013","journal-title":"Nat. Immunol."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib93","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nn.4528","article-title":"Regulatory T cells promote myelin regeneration in the central nervous system","volume":"20","author":"Dombrowski","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.phrs.2025.108041_bib94","first-page":"654","article-title":"Inducing and administering tregs to treat human disease","volume":"6","author":"Perdigoto","year":"2015","journal-title":"Front Immunol."},{"key":"10.1016\/j.phrs.2025.108041_bib95","doi-asserted-by":"crossref","first-page":"1166135","DOI":"10.3389\/fimmu.2023.1166135","article-title":"Opportunities for Treg cell therapy for the treatment of human disease","volume":"14","author":"Bluestone","year":"2023","journal-title":"Front Immunol."},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib96","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1084\/jem.20082824","article-title":"In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression","volume":"206","author":"Webster","year":"2009","journal-title":"J. Exp. Med"},{"key":"10.1016\/j.phrs.2025.108041_bib97","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fimmu.2019.00043","article-title":"Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity","volume":"10","author":"Romano","year":"2019","journal-title":"Front Immunol."},{"key":"10.1016\/j.phrs.2025.108041_bib98","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1146\/annurev-immunol-042617-053055","article-title":"Translating Immunology into Therapeutic Concepts for Inflammatory Bowel Disease","volume":"36","author":"Uhlig","year":"2018","journal-title":"Annu Rev. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib99","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2019.12.002","article-title":"Precursors for nonlymphoid-tissue treg cells reside in secondary lymphoid organs and are programmed by the transcription factor BATF","volume":"52","author":"Delacher","year":"2020","journal-title":"Immunity"},{"issue":"7","key":"10.1016\/j.phrs.2025.108041_bib100","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.immuni.2024.05.023","article-title":"The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program","volume":"57","author":"Burton","year":"2024","journal-title":"Immunity"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib101","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.06.026","article-title":"Microglia Require CD4 T cells to complete the fetal-to-adult transition","volume":"182","author":"Pasciuto","year":"2020","journal-title":"Cell"},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib102","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41577-021-00519-w","article-title":"Tissue regulatory T cells: regulatory chameleons","volume":"21","author":"Mu\u00f1oz-Rojas","year":"2021","journal-title":"Nat. Rev. Immunol."},{"issue":"7404","key":"10.1016\/j.phrs.2025.108041_bib103","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature11132","article-title":"PPAR-\u03b3 is a major driver of the accumulation and phenotype of adipose tissue Treg cells","volume":"486","author":"Cipolletta","year":"2012","journal-title":"Nature"},{"issue":"100","key":"10.1016\/j.phrs.2025.108041_bib104","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jaut.2013.06.006","article-title":"Treg and CTLA-4: two intertwining pathways to immune tolerance","volume":"45","author":"Walker","year":"2013","journal-title":"J. Autoimmun."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib105","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/eji.200425810","article-title":"CD40\/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2","volume":"35","author":"Guiducci","year":"2005","journal-title":"Eur. J. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib106","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10067-019-04768-y","article-title":"Alterations in peripheral T cell and B cell subsets in patients with osteoarthritis","volume":"39","author":"Zhu","year":"2020","journal-title":"Clin. Rheuma"},{"issue":"11","key":"10.1016\/j.phrs.2025.108041_bib107","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1016\/j.joca.2015.06.018","article-title":"Changes in peripheral blood immune cell composition in osteoarthritis","volume":"23","author":"Ponchel","year":"2015","journal-title":"Osteoarthr. Cartil."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib108","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s10020-021-00315-1","article-title":"MiR-206 regulates the Th17\/Treg ratio during osteoarthritis","volume":"27","author":"Ye","year":"2021","journal-title":"Mol. Med"},{"key":"10.1016\/j.phrs.2025.108041_bib109","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.biopha.2016.01.036","article-title":"Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated with a reduction in Tim-3 expression","volume":"79","author":"Li","year":"2016","journal-title":"Biomed. Pharm."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib110","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1089\/dna.2017.3771","article-title":"Overexpression of Lymphocyte Activation Gene-3 Inhibits Regulatory T Cell Responses in Osteoarthritis","volume":"36","author":"Xia","year":"2017","journal-title":"DNA Cell Biol."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib111","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1080\/08923973.2018.1523927","article-title":"Suppressive oligodeoxynucleotide-induced dendritic cells rein the aggravation of osteoarthritis in mice","volume":"40","author":"Guo","year":"2018","journal-title":"Immunopharmacol. Immunotoxicol."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib112","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-32206-7","article-title":"Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10","volume":"8","author":"Kwon","year":"2018","journal-title":"Sci. Rep."},{"issue":"47","key":"10.1016\/j.phrs.2025.108041_bib113","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abo5284","article-title":"Tolerogenic nanoparticles induce type II collagen-specific regulatory T cells and ameliorate osteoarthritis","volume":"8","author":"Sohn","year":"2022","journal-title":"Sci. Adv."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib114","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1080\/02656736.2018.1502896","article-title":"Innate\/inflammatory bioregulation and clinical effectiveness of whole-body hyperthermia (balneotherapy) in elderly patients with osteoarthritis","volume":"35","author":"G\u00e1lvez","year":"2018","journal-title":"Int J. Hyperth."},{"key":"10.1016\/j.phrs.2025.108041_bib115","doi-asserted-by":"crossref","first-page":"1247710","DOI":"10.3389\/fimmu.2023.1247710","article-title":"Causal relationships between CD25 on immune cells and hip osteoarthritis","volume":"14","author":"Luo","year":"2023","journal-title":"Front Immunol."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib116","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a040501","article-title":"Mendelian Randomization: Concepts and Scope","volume":"12","author":"Richmond","year":"2022","journal-title":"Cold Spring Harb. Perspect. Med"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib117","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1177\/03635465231153588","article-title":"T Helper 17-Like Regulatory T cells in equine synovial fluid are associated with disease severity of naturally occurring posttraumatic osteoarthritis","volume":"51","author":"Keller","year":"2023","journal-title":"Am. J. Sports Med"},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib118","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1172\/JCI57175","article-title":"Control of inflammation by integration of environmental cues by regulatory T cells","volume":"123","author":"Chaudhry","year":"2013","journal-title":"J. Clin. Invest"},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib119","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.immuni.2008.05.007","article-title":"Molecular antagonism and plasticity of regulatory and inflammatory T cell programs","volume":"29","author":"Yang","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.phrs.2025.108041_bib120","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1016\/j.joca.2017.02.147","article-title":"High synovial fluid interleukin-6 levels are associated with increased matrix metalloproteinase levels and severe radiographic changes in osteoarthritis patients","volume":"25","author":"Vuolteenaho","year":"2017","journal-title":"Osteoarthr. Cartil."},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib121","doi-asserted-by":"crossref","first-page":"478","DOI":"10.2106\/JBJS.N.00200","article-title":"Inflammatory cytokine response following acute tibial plateau fracture","volume":"97","author":"Haller","year":"2015","journal-title":"J. Bone Jt. Surg. Am."},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib122","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/art.23495","article-title":"Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury","volume":"58","author":"Elsaid","year":"2008","journal-title":"Arthritis Rheum. Off. J. Am. Coll. Rheumatol."},{"key":"10.1016\/j.phrs.2025.108041_bib123","first-page":"356","article-title":"T cells in osteoarthritis: alterations and beyond","volume":"8","author":"Li","year":"2017","journal-title":"Front Immunol."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib124","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.3390\/jcm9082423","article-title":"T helper cell infiltration in osteoarthritis-related knee pain and disability","volume":"9","author":"Nees","year":"2020","journal-title":"J. Clin. Med."},{"issue":"18","key":"10.1016\/j.phrs.2025.108041_bib125","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1182\/blood-2008-10-183251","article-title":"IL-17-producing human peripheral regulatory T cells retain suppressive function","volume":"113","author":"Beriou","year":"2009","journal-title":"Blood"},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib126","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1073\/pnas.0900408106","article-title":"Identification of IL-17-producing FOXP3+ regulatory T cells in humans","volume":"106","author":"Voo","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib127","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1136\/annrheumdis-2013-204228","article-title":"Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood","volume":"74","author":"Wang","year":"2015","journal-title":"Ann. Rheum. Dis."},{"issue":"6602","key":"10.1016\/j.phrs.2025.108041_bib128","doi-asserted-by":"crossref","DOI":"10.1126\/science.abg9302","article-title":"Interleukin-17 governs hypoxic adaptation of injured epithelium","volume":"377","author":"Konieczny","year":"2022","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib129","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.4049\/jimmunol.1200413","article-title":"IFN-\u03b3 production by allogeneic Foxp3+ regulatory T cells is essential for preventing experimental graft-versus-host disease","volume":"189","author":"Koenecke","year":"2012","journal-title":"J. Immunol."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib130","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00005-016-0399-5","article-title":"CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients","volume":"64","author":"\u017babi\u0144ska","year":"2016","journal-title":"Arch. Immunol. Ther. Exp. (Warsz. )"},{"key":"10.1016\/j.phrs.2025.108041_bib131","series-title":"Seminars in Arthritis and Rheumatism","first-page":"91","article-title":"Arthroscopic and synovial correlates of pain in osteoarthritis","author":"Lindblad","year":"1989"},{"issue":"14","key":"10.1016\/j.phrs.2025.108041_bib132","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.1073\/pnas.1312717110","article-title":"Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation","volume":"111","author":"Morikawa","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib133","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/ni1318","article-title":"An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires","volume":"7","author":"Hsieh","year":"2006","journal-title":"Nat. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib134","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.immuni.2004.07.009","article-title":"Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors","volume":"21","author":"Hsieh","year":"2004","journal-title":"Immunity"},{"issue":"6124","key":"10.1016\/j.phrs.2025.108041_bib135","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1126\/science.1233913","article-title":"Aire-dependent thymic development of tumor-associated regulatory T cells","volume":"339","author":"Malchow","year":"2013","journal-title":"Science"},{"issue":"11","key":"10.1016\/j.phrs.2025.108041_bib136","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ni.3004","article-title":"Continuous requirement for the TCR in regulatory T cell function","volume":"15","author":"Levine","year":"2014","journal-title":"Nat. Immunol."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib137","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.immuni.2014.10.012","article-title":"Continuous T cell receptor signals maintain a functional regulatory T cell pool","volume":"41","author":"Vahl","year":"2014","journal-title":"Immunity"},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib138","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2013.10.054","article-title":"A special population of regulatory T cells potentiates muscle repair","volume":"155","author":"Burzyn","year":"2013","journal-title":"Cell"},{"issue":"7738","key":"10.1016\/j.phrs.2025.108041_bib139","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41586-018-0824-5","article-title":"Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery","volume":"565","author":"Ito","year":"2019","journal-title":"Nature"},{"issue":"20","key":"10.1016\/j.phrs.2025.108041_bib140","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1161\/CIRCULATIONAHA.120.046789","article-title":"A unique population of regulatory T cells in heart potentiates cardiac protection from myocardial infarction","volume":"142","author":"Xia","year":"2020","journal-title":"Circulation"},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib141","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41590-018-0280-2","article-title":"Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells","volume":"20","author":"Akkaya","year":"2019","journal-title":"Nat. Immunol."},{"issue":"3","key":"10.1016\/j.phrs.2025.108041_bib142","doi-asserted-by":"crossref","DOI":"10.1016\/j.ocarto.2021.100193","article-title":"Regulatory T cells provide chondroprotection through increased TIMP1, IL-10 and IL-4, but cannot mitigate the catabolic effects of IL-1\u03b2 and IL-6 in a tri-culture model of osteoarthritis","volume":"3","author":"Keller","year":"2021","journal-title":"Osteoarthr. Cartil. Open"},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib143","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/jor.25453","article-title":"Interleukin-6 neutralization and regulatory T cells are additive in chondroprotection from IL-1\u03b2-induced inflammation","volume":"41","author":"Keller","year":"2023","journal-title":"J. Orthop. Res"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib144","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41577-019-0240-6","article-title":"Efferocytosis in health and disease","volume":"20","author":"Doran","year":"2020","journal-title":"Nat. Rev. Immunol."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib145","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/art.42412","article-title":"Impaired Efferocytosis by Synovial Macrophages in Patients With Knee Osteoarthritis","volume":"75","author":"Del Sordo","year":"2023","journal-title":"Arthritis Rheuma"},{"key":"10.1016\/j.phrs.2025.108041_bib146","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.83069","article-title":"Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis","volume":"12","author":"Yao","year":"2023","journal-title":"Elife"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib147","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.immuni.2018.07.015","article-title":"Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution","volume":"49","author":"Proto","year":"2018","journal-title":"Immunity"},{"key":"10.1016\/j.phrs.2025.108041_bib148","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13075-015-0833-9","article-title":"Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes","volume":"17","author":"Hwang","year":"2015","journal-title":"Arthritis Res Ther."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib149","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.joca.2005.04.017","article-title":"Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin fragments in human articular chondrocytes","volume":"13","author":"Su","year":"2005","journal-title":"Osteoarthr. Cartil."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib150","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1172\/JCI23755","article-title":"The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages","volume":"115","author":"Schaefer","year":"2005","journal-title":"J. Clin. Invest"},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib151","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1002\/art.39063","article-title":"Bioactivity in an Aggrecan 32-mer Fragment Is Mediated via Toll-like Receptor 2","volume":"67","author":"Lees","year":"2015","journal-title":"Arthritis Rheuma"},{"issue":"4","key":"10.1016\/j.phrs.2025.108041_bib152","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.celrep.2019.12.083","article-title":"Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration","volume":"30","author":"Piao","year":"2020","journal-title":"Cell Rep."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib153","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10456-013-9393-2","article-title":"The effects of inflammatory cytokines on lymphatic endothelial barrier function","volume":"17","author":"Cromer","year":"2014","journal-title":"Angiogenesis"},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib154","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.joca.2022.04.003","article-title":"Role of synovial lymphatic function in osteoarthritis","volume":"30","author":"Cao","year":"2022","journal-title":"Osteoarthr. Cartil."},{"issue":"5","key":"10.1016\/j.phrs.2025.108041_bib155","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A Distinct Function of Regulatory T cells in tissue protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.phrs.2025.108041_bib156","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.celrep.2018.07.019","article-title":"Regulatory T cells promote apelin-mediated sprouting angiogenesis in type 2 diabetes","volume":"24","author":"Leung","year":"2018","journal-title":"Cell Rep."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib157","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1165\/rcmb.2017-0019OC","article-title":"Foxp3(+) Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation","volume":"57","author":"Dial","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib158","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.it.2012.07.007","article-title":"Application of IL-2 therapy to target T regulatory cell function","volume":"33","author":"Shevach","year":"2012","journal-title":"Trends Immunol."},{"issue":"10","key":"10.1016\/j.phrs.2025.108041_bib159","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/s41577-018-0046-y","article-title":"Biology and regulation of IL-2: from molecular mechanisms to human therapy","volume":"18","author":"Spolski","year":"2018","journal-title":"Nat. Rev. Immunol."},{"issue":"12","key":"10.1016\/j.phrs.2025.108041_bib160","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41584-021-00707-x","article-title":"Interleukin-2 and regulatory T cells in rheumatic diseases","volume":"17","author":"Kolios","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.phrs.2025.108041_bib161","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2023.12.019","article-title":"Niche-specific control of tissue function by regulatory T cells\u2014current challenges and perspectives for targeting metabolic disease","author":"Becker","year":"2024","journal-title":"Cell Metab."},{"key":"10.1016\/j.phrs.2025.108041_bib162","doi-asserted-by":"crossref","first-page":"1090721","DOI":"10.3389\/fmed.2023.1090721","article-title":"Barriers to Treg therapy in Europe: From production to regulation","volume":"10","author":"Hennessy","year":"2023","journal-title":"Front Med (Lausanne)"},{"issue":"40","key":"10.1016\/j.phrs.2025.108041_bib163","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aaw2707","article-title":"Conversion of antigen-specific effector\/memory T cells into Foxp3-expressing T(reg) cells by inhibition of CDK8\/19","volume":"4","author":"Akamatsu","year":"2019","journal-title":"Sci. Immunol."},{"issue":"2","key":"10.1016\/j.phrs.2025.108041_bib164","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/imcb.12613","article-title":"Regulatory T-cell stability and functional plasticity in health and disease","volume":"101","author":"Malviya","year":"2023","journal-title":"Immunol. Cell Biol."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib165","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/jleuko\/qiae049","article-title":"Stability and plasticity of regulatory T cells in health and disease","volume":"116","author":"Contreras-Castillo","year":"2024","journal-title":"J. Leukoc. Biol."},{"issue":"9","key":"10.1016\/j.phrs.2025.108041_bib166","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/ni.1774","article-title":"Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo","volume":"10","author":"Zhou","year":"2009","journal-title":"Nat. Immunol."},{"issue":"8","key":"10.1016\/j.phrs.2025.108041_bib167","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1002\/eji.202049123","article-title":"Mechanisms of exTreg induction","volume":"51","author":"Saxena","year":"2021","journal-title":"Eur. J. Immunol."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib168","doi-asserted-by":"crossref","first-page":"7644","DOI":"10.1038\/s41467-025-62628-7","article-title":"Regulatory T cell therapy promotes TGF-\u03b2 and IL-6-dependent pro-inflammatory Th17 cell generation by reducing IL-2","volume":"16","author":"Cheng","year":"2025","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.phrs.2025.108041_bib169","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2024.101211","article-title":"Rationally engineered novel AAV capsids for intra-articular gene delivery","volume":"32","author":"Li","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825004669?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825004669?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T23:46:49Z","timestamp":1766188009000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661825004669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":169,"alternative-id":["S1043661825004669"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2025.108041","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Adaptive immunity in osteoarthritis: Mechanisms and opportunities for regulatory T-cell\u2013targeted therapy","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2025.108041","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108041"}}