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Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR Interaction

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 cocultur...

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Detalles Bibliográficos
Autores principales: Kim, Sung Hoon, Youn, Jeehee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Association of Immunologists 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509167/
https://www.ncbi.nlm.nih.gov/pubmed/23213316
http://dx.doi.org/10.4110/in.2012.12.5.217
Descripción
Sumario: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.