Prolyl hydroxylase 3 (PHD3) expression augments the development of regulatory T cells

Yogesh Singh; Xiaolong Shi; Shaqiu Zhang; Anja T Umbach; Hong Chen; Madhuri S Salker; Florian Lang

doi:10.1016/j.molimm.2016.06.003

Prolyl hydroxylase 3 (PHD3) expression augments the development of regulatory T cells

Mol Immunol. 2016 Aug:76:7-12. doi: 10.1016/j.molimm.2016.06.003. Epub 2016 Jun 19.

Authors

Yogesh Singh¹, Xiaolong Shi², Shaqiu Zhang³, Anja T Umbach², Hong Chen², Madhuri S Salker², Florian Lang⁴

Affiliations

¹ Departments of Cardiology, Vascular Medicine and Physiology, Eberhard Karls University of Tubingen, Gmelinstraβe 5, D-72076 Tubingen, Germany. Electronic address: [email protected].
² Departments of Cardiology, Vascular Medicine and Physiology, Eberhard Karls University of Tubingen, Gmelinstraβe 5, D-72076 Tubingen, Germany.
³ Departments of Cardiology, Vascular Medicine and Physiology, Eberhard Karls University of Tubingen, Gmelinstraβe 5, D-72076 Tubingen, Germany; Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, 611130, PR China.
⁴ Departments of Cardiology, Vascular Medicine and Physiology, Eberhard Karls University of Tubingen, Gmelinstraβe 5, D-72076 Tubingen, Germany. Electronic address: [email protected].

PMID: 27331863
DOI: 10.1016/j.molimm.2016.06.003

Abstract

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.

Keywords: DMOG; HIF-1α; PHD3; Th17; Tregs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / immunology*
Cell Separation
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Knockdown Techniques
Immunoblotting
Mice
Mice, Inbred C57BL
Polymerase Chain Reaction
Procollagen-Proline Dioxygenase / immunology*
T-Lymphocytes, Regulatory / immunology*

Substances

PHD3 protein, mouse
Procollagen-Proline Dioxygenase