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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\u2013mediated (IDO1-mediated) tryptophan depletion as the primary driver of FLS-induced T cell hyporesponsiveness. Spatial transcriptomics revealed colocalization of\n                    <jats:italic>IDO1<\/jats:italic>\n                    and\n                    <jats:italic>CD69<\/jats:italic>\n                    within ectopic lymphoid structures in RA synovium, further supporting the in vivo relevance of this pathway. These findings provide the groundwork for positioning FLS as critical T cell regulators in RA and highlight the importance of preserving their immunosuppressive properties when therapeutically targeting pathogenic FLS functions.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.193054","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T16:00:19Z","timestamp":1759852819000},"source":"Crossref","is-referenced-by-count":11,"title":["Rheumatoid arthritis synovial fibroblasts modulate T cell activation"],"prefix":"10.1172","volume":"10","author":[{"given":"Melissa R.","family":"Romoff","sequence":"first","affiliation":[{"name":"Research Institute, Hospital for Special Surgery, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preethi K.","family":"Periyakoil","sequence":"additional","affiliation":[{"name":"Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, 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