A PHD in immunosuppression: oxygen-sensing pathways regulate immunosuppressive Tregs
Weiping Zou, Yatrik M. Shah
Weiping Zou, Yatrik M. Shah
Published July 29, 2019
Citation Information: J Clin Invest. 2019;129(9):3524-3526. https://doi.org/10.1172/JCI130009.
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A PHD in immunosuppression: oxygen-sensing pathways regulate immunosuppressive Tregs

Abstract

The oxygen-sensing prolyl hydroxylase domain (PHD) enzymes are key to maintaining tissue homeostasis during hypoxia via their regulation of the expression and activity of HIF, the master transcription factor for the hypoxic response. In this issue of the JCI, Yamamoto, Hester, and colleagues show that temporal and reversible inhibition of PHD2 in vivo leads to systemic autoimmune disorder. The work demonstrates that a reduction of PHD2 leads to impairment of immunosuppressive Treg function via a HIF2α-dependent mechanism, without altering Foxp3 expression. This study indicates that a PHD2/HIF2α axis is critical for maintaining proper Treg function.

Authors

Weiping Zou, Yatrik M. Shah

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Figure 1

Transgenic loss of PHD2 results in autoimmunity.

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Transgenic loss of PHD2 results in autoimmunity. In the presence of doxy...
In the presence of doxycycline, transgenic mice show increased expression of shRNA for PHD2 in all tissues. shRNA for PHD2 (shPhd2) stabilizes HIF2α in the hemopoietic compartment, leading to complete loss of the immunosuppressive function of Tregs. No changes in Foxp3 expression or Treg numbers, but an increase in T-bet and TNF-α expression, were observed following shPhd2 expression. The mice had a progressive autoimmune disorder, which was completely reversible following the removal of doxycycline (DOX). CAG, chicken β-actin.