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New findings from Peter Ratcliffe's and Chris Pugh's research groups.

Low oxygen levels (hypoxia) are sensed by prolyl hydroxylase (PHD) enzymes that mediate the body’s responses via hypoxia-inducible factors 1 and 2 (HIFs). Previous studies have reported a link between oxygen sensing and immune/inflammatory pathways, but these results were complicated by the genetic experimental tools used. Joanna Hester and Ludwig Oxford’s Atsushi Yamamoto from Peter Ratcliffe’s and Chris Pugh’s groups have used more sophisticated timed and reversible PHD gene silencing to study the importance of oxygen sensing on immune regulation. Their paper, published in The Journal of Clinical Investigation shows that PHD2 regulates immune cell activity via HIF2 but not HIF1. This discovery has medical significance since PHD2 and HIF2 inhibitors are currently in clinical trials for anaemia and renal cancer respectively.