Rheumatoid arthritis synovial fibroblasts modulate T cell activation.

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

SUBMITTER: Romoff MR 

PROVIDER: S-EPMC12643496 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature