{"doi":"10.3390/jcm15020658","title":"Understanding the Inflammatory Aspect of Osteoarthritis: Lessons from Immune Checkpoint Inhibitors","abstract":"<jats:p>Osteoarthritis (OA) is the most prevalent form of arthritis and is a major global health burden. OA is a heterogeneous condition with multiple contributing mechanisms that characterize different subtypes and stages of the disease. In this review, we examine the insights gained into the immunological characteristics of OA that have emerged from the increasingly widespread use of checkpoint inhibitors in the immunotherapy of malignancies. We discuss how the conventional view of OA as a degenerative disease is changing in view of the evidence suggesting that OA has an inflammatory component along with the presence in joint tissue of peripherally tolerized autoreactive resident memory T cells, which upon release of their inhibition by immunotherapy mediate immune-related adverse event arthritis (irAE-arthritis). We review clinical trials evaluating the efficacy of immunosuppressive therapies in modifying the course of OA, thereby providing an additional perspective on the presence and nature of the inflammation in OA. In summary, we argue that a shift from the traditional understanding of OA as a mechanical disease to one that incorporates the role of synovial immune cells and mechanisms of self-tolerance is necessary to guide future therapies, including the use of immune checkpoints for patients with OA.</jats:p>","journal":"Journal of Clinical Medicine","year":2026,"id":606506,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":950374,"name":"Matthieu Paiola","orcid":"0000-0002-3536-861X","position":1,"is_corresponding":false},{"id":899874,"name":"Carly Tymm","orcid":"0000-0003-2682-4051","position":2,"is_corresponding":false},{"id":56237,"name":"Robert Winchester","orcid":"0000-0002-7543-8037","position":3,"is_corresponding":false},{"id":672412,"name":"Adam Mor","orcid":"0000-0002-1065-2999","position":4,"is_corresponding":false},{"id":672411,"name":"Yevgeniya Gartshteyn","orcid":"0000-0001-5547-4658","position":5,"is_corresponding":false},{"id":1557041,"name":"Daniel M. Portnoy","orcid":"0009-0002-7548-3548","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Understanding the Inflammatory Aspect of Osteoarthritis: Lessons from Immune Checkpoint Inhibitors","abstract":"<jats:p>Osteoarthritis (OA) is the most prevalent form of arthritis and is a major global health burden. OA is a heterogeneous condition with multiple contributing mechanisms that characterize different subtypes and stages of the disease. In this review, we examine the insights gained into the immunological characteristics of OA that have emerged from the increasingly widespread use of checkpoint inhibitors in the immunotherapy of malignancies. We discuss how the conventional view of OA as a degenerative disease is changing in view of the evidence suggesting that OA has an inflammatory component along with the presence in joint tissue of peripherally tolerized autoreactive resident memory T cells, which upon release of their inhibition by immunotherapy mediate immune-related adverse event arthritis (irAE-arthritis). We review clinical trials evaluating the efficacy of immunosuppressive therapies in modifying the course of OA, thereby providing an additional perspective on the presence and nature of the inflammation in OA. In summary, we argue that a shift from the traditional understanding of OA as a mechanical disease to one that incorporates the role of synovial immune cells and mechanisms of self-tolerance is necessary to guide future therapies, including the use of immune checkpoints for patients with OA.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41598595","pmcid":"PMC12841676","openalex_id":null,"authors":[],"funders":[{"funder_name":"National Institute of Health","grant_id":"R01AI150597 (AM)","title":null},{"funder_name":"National Institute of Health","grant_id":"R01AI125640 (AM)","title":null},{"funder_name":"National Institute of Health","grant_id":"R01AI175498 (AM)","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI125640","title":null},{"funder_name":"HHS","grant_id":"R01AI150597 R01AI125640, and R01AI175498","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI150597","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI175498","title":null}],"total_grants":7,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2077-0383/15/2/658/pdf?version=1768381479","host_type":"publisher"},{"url":"https://www.mdpi.com/2077-0383/15/2/658/pdf","host_type":"publisher"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12841676/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12841676","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12841676?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":[],"keywords":["Immunotherapy","Osteoarthritis","Immune-related Adverse Events"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T04:41:04.550218Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}