Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR Interaction.
- Author:
Sung Hoon KIM
1
;
Jeehee YOUN
Author Information
- Publication Type:Brief Communication
- Keywords: Autoimmune arthritis; Regulatory T cells; Fibroblast-like synoviocytes; Foxp3
- MeSH: Animals; Arthritis; Hand; Inflammation; Interleukin-6; Leukocytes; Licensure; Mice; Receptors, Tumor Necrosis Factor; Synovial Fluid; T-Lymphocytes, Regulatory
- From:Immune Network 2012;12(5):217-221
- CountryRepublic of Korea
- Language:English
- Abstract: Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.
