{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Romoff MR"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","NHGRI NIH HHS","NIAMS NIH HHS","National Institute of General Medical Sciences","National Human Genome Research Institute","NIGMS NIH HHS"],"pagination":["e193054"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12643496"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(22)"],"pubmed_abstract":["In the rheumatoid arthritis (RA) synovium, resident fibroblast-like synoviocytes (FLS) express MHC class II molecules (HLA-D) but lack the costimulatory signals typically required for T cell activation. Here, we demonstrate that antigen presentation by FLS induces a distinct T cell activation state characterized by high CD69 yet reduced CD25 and HLA-DR expression, suppressed proliferation, and decreased effector cytokine production compared with professional antigen-presenting cells (APCs), such as macrophages. FLS were also capable of suppressing macrophage-induced T cell activation, underscoring their dominant immunomodulatory role in the synovial microenvironment. Mechanistically, we identify indoleamine 2,3-dioxygenase-mediated (IDO1-mediated) tryptophan depletion as the primary driver"],"journal":["JCI insight"],"pubmed_title":["Rheumatoid arthritis synovial fibroblasts modulate T cell activation."],"pmcid":["PMC12643496"],"funding_grant_id":["AI034206-28","U01 HG012103","R37 AI034206","T32 AR071302","T32 5T32AR071302-04","R01 AI148435","R01 AI034206","AI148435","T32GM152349","T32 GM152349"],"pubmed_authors":["Smith MH","DiCarlo EF","Periyakoil PK","Ramirez D","Leslie CS","Goodman SM","Donlin LT","Rudensky AY","Romoff MR"],"additional_accession":[]},"is_claimable":false,"name":"Rheumatoid arthritis synovial fibroblasts modulate T cell activation.","description":"In the rheumatoid arthritis (RA) synovium, resident fibroblast-like synoviocytes (FLS) express MHC class II molecules (HLA-D) but lack the costimulatory signals typically required for T cell activation. Here, we demonstrate that antigen presentation by FLS induces a distinct T cell activation state characterized by high CD69 yet reduced CD25 and HLA-DR expression, suppressed proliferation, and decreased effector cytokine production compared with professional antigen-presenting cells (APCs), such as macrophages. FLS were also capable of suppressing macrophage-induced T cell activation, underscoring their dominant immunomodulatory role in the synovial microenvironment. Mechanistically, we identify indoleamine 2,3-dioxygenase-mediated (IDO1-mediated) tryptophan depletion as the primary driver","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T18:41:07.573Z","creation":"2026-05-20T03:13:32.917Z"},"accession":"S-EPMC12643496","cross_references":{"pubmed":["41055954"],"doi":["10.1172/jci.insight.193054"]}}