KMID : 0923620120120050217
|
|
Immune Network 2012 Volume.12 No. 5 p.217 ~ p.221
|
|
Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR Interaction
|
|
Kim Sung-Hoon
Youn Jee-Hee
|
|
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.
|
|
KEYWORD
|
|
Autoimmune arthritis, Regulatory T cells, Fibroblast-like synoviocytes, Foxp3
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|