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Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR
1Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea.
Immune Network
|December 6, 2012
Summary
Inflamed fibroblast-like synoviocytes (FLS) interact with regulatory T cells (Tregs) via GITRL/GITR, reducing Treg function and increasing FLS-driven IL-6 production, worsening inflammatory arthritis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Fibroblast-like synoviocytes (FLS) are present in rheumatoid arthritis synovium.
- Leukocyte infiltration amplifies inflammation by signaling to FLS.
- Crosstalk between FLS and regulatory T cells (Tregs) is not well understood.
Purpose of the Study:
- To investigate the interaction between FLS and Tregs in inflammatory arthritis.
- To characterize the functional consequences of FLS-Treg crosstalk.
Main Methods:
- Coculture of FLS lines from arthritic mice with Tregs.
- Assessment of Foxp3 and GITR expression in Tregs.
- Evaluation of IL-6 production by FLS.
- Use of blocking antibodies against GITR.
Main Results:
- FLS expressing GITR ligand (GITRL) reduced Treg Foxp3 and GITR expression in a contact-dependent manner.
- This reduction was abrogated by anti-GITR antibody.
- Tregs induced increased IL-6 production by FLS.
Conclusions:
- Inflamed FLS downregulate Treg anti-inflammatory function via GITRL/GITR.
- Tregs enhance FLS pro-inflammatory activity by increasing IL-6 production.
- FLS-Treg interaction exacerbates inflammatory arthritis.
- This interaction dampens Treg anti-inflammatory activity and amplifies FLS pro-inflammatory activity, worsening inflammatory arthritis.
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