Rheumatoid arthritis synovial fibroblast modulation of T cell activation

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B570
Abstract ID: 6493

Presenting Author:
Melissa Romoff , Post-bacc Researcher at Hosp. for Special Surgery, Weill Cornell Medical College

Abstract:

Rheumatoid arthritis (RA), a systemic autoimmune disorder with predominantly articular manifestations, is histologically characterized by hyperplasia and leukocyte infiltration of the synovium (joint lining). Here, we investigated crosstalk between tissue-resident synovial fibroblasts (FLS) and infiltrating T cells. Using paired single-cell RNA and ATAC sequencing of primary human FLS and FLS-specific cytokine response gene signatures, we identified a population of FLS responsive to IFNg+TNFa, predicated to originate from activated T cells. Spatial histology of patient joints detected a subset of FLS with high levels of phosphorylated STAT1+, a marker of IFNg-responsivity. These FLS localized within T cell aggregates and expressed HLA-DR, indicating these resident stromal cells are equipped to directly modify CD4 T cells through antigen presentation. Using staphylococcal enterotoxin B (SEB) to promote MHC class II-dependent interactions, FLS resulted in enhanced CD69 expression on CD4 T cells while suppressing proliferation relative to cultures in which macrophages functioned as the antigen-presenting cells. In summary, we demonstrate that FLS in the RA synovium can be activated by infiltrating T cells, wherein the fibroblasts are then equipped to suppress T cell proliferation in an MHC class II-dependent manner. Our work supports a central role for FLS in regulating T cell responses, which have likely become overwhelmed and deregulated in autoimmune RA joints.