Session Information
Date: Monday, October 27, 2025
Title: (0978–1006) T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster
Session Type: Poster Session B
Session Time: 10:30AM-12:30PM
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint specific memory. We previously demonstrated that joint-specific memory is mediated by CD8+ synovial resident memory T (TRM) cells that persist in arthritic joints during remission and can mediate arthritis flares. Further, we found that fibroblast-like synoviocytes (FLS) facilitate the formation of TRM through IL-15 production. As cell-cell interactions can be bidirectional, we investigated the effects of TRM on FLS pathogenicity.
Methods: TRM were generated through two-week co-culture with FLS isolated from RA synovium in the presence of IL-15. TRM development was validated by cell surface markers, gene expression profile and enhanced Bodipy free fatty acid uptake. TRM were purified through multi-step magnetic nanobead sorting for CD62L-, CD25- and CD69+ cells. Purified TRM cells were stimulated with anti-CD3/CD28 dynabeads for 24 hours then co-cultured with new unstimulated FLS. After 48 to 72 hours, FLS were collected and assayed for phenotypic markers of cellular activation by flow cytometry, for pathogenic gene expression by qPCR, and for protein expression by ELISA.
Results: TRM generated through FLS co-culture displayed surface phenotype CD45RO+CD62L-CCR7-HLA-DR-CD25-CD69+ with variable CD103 and CD49a expression. These cells also displayed enhanced free fatty uptake and a gene expression signature consistent with TRM. FLS co-cultured with purified TRM upregulated surface expression of HLA-DR and ICAM-1 similar to FLS stimulated with TNF alone. TRM-stimulated FLS also increased expression of inflammatory cytokines (IL-6, IL-8), chemokines (CCL5) and matrix metalloproteinases (MMP1, MMP3).
Conclusion: We previously showed that FLS facilitate synovial TRM development. We now demonstrate that TRM also promote FLS activation, stimulating the expression of inflammatory cytokines, chemokines and matrix metalloproteinases by FLS, thus contributing to arthritis pathogenesis.
To cite this abstract in AMA style:
Mangin M, Yang Y, Miyashita Y, Chang M. Resident Memory T Cells Stimulate Pathogenic Activity in Fibroblast-like Synoviocytes [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/resident-memory-t-cells-stimulate-pathogenic-activity-in-fibroblast-like-synoviocytes/. Accessed .« Back to ACR Convergence 2025
ACR Meeting Abstracts - https://acrabstracts.org/abstract/resident-memory-t-cells-stimulate-pathogenic-activity-in-fibroblast-like-synoviocytes/