{"doi":"10.1126/sciimmunol.adm7800","title":"T <sub>H</sub> 17 cells converted into exT <sub>H</sub> 17 cells sustain rheumatoid-like IL-17–independent inflammatory arthritis","abstract":"T helper 17 (T H 17) cells are found in the periphery and synovium of patients with rheumatoid arthritis (RA); however, IL-17–targeted interventions have limited efficacy in established RA. Inflammation can induce T H 17 cell transdifferentiation into IL-17–negative exT H 17 cells, but the role of exT H 17 cells in arthritis is unknown. We performed T H 17 cell lineage tracing in the SKG mouse model of RA. In arthritic mice, synovial T H 17 cells transdifferentiate into CD44 + exT H 17 cells, which are more arthritogenic and sustain inflammation that is IL-17 independent. The exT H 17 cell gene signature includes up-regulation of CD44 and sphingosine-1-phosphate receptor 4 (S1PR4) and correlates with the profile of human RA synovial CD4 + T cells. We demonstrate that cross-talk between T H 17 cells and fibroblast-like synoviocytes (FLSs) via S1P promotes T H 17-exT H 17 cell conversion. CD44 is necessary for exT H 17 cell–mediated arthritis. Our study suggests that FLS expansion during RA progression promotes T H 17-exT H 17 cell conversion. These results could potentially enable RA precision therapy.","journal":"Science Immunology","year":2025,"id":520233,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1079664,"name":"Kensuke Suga","orcid":"0000-0003-3107-788X","position":1,"is_corresponding":false},{"id":471531,"name":"Amara Seng","orcid":"0000-0001-7077-5969","position":2,"is_corresponding":false},{"id":361518,"name":"Mattias N. 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