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Regulatory T cells (Tregs) are required for effective immune homeostasis by suppressing harmful immune responses against self-antigens. Transcription factor Foxp3 is required for the development of these cells. How Foxp3 is stabilised and affects Tregs development is still incompletely understood. Previous studies have suggested that hypoxia inducible factor gene HIF-1α negatively influences the development of Tregs and enhances the development of IL-17 producing Th17 cells. In this study, we reveal that prolyl hydroxylase 3 (PHD3), which is a negative regulator of HIF-1α, is upregulated in Tregs and enhances the development of Tregs. The PHD3 inhibitor dimethyl oxalylglycine (DMOG) or siRNAs-PHD3, which upregulates HIF-1α, down-regulated Foxp3 expression, and enhanced the development of Th17 cells. Our observations disclose a novel role of PHD3 in the development of Tregs.

More information Original publication

DOI

10.1016/j.molimm.2016.06.003

Type

Journal article

Publication Date

2016-08-01T00:00:00+00:00

Volume

76

Pages

7 - 12

Total pages

5

Keywords

DMOG, HIF-1α, PHD3, Th17, Tregs, Animals, Cell Differentiation, Cell Separation, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Gene Knockdown Techniques, Immunoblotting, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, Procollagen-Proline Dioxygenase, T-Lymphocytes, Regulatory