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Cutting edge: Hypoxia-inducible factor 1 negatively regulates Th1 function

By Hussein Shehade, Valérie Acolty, Muriel Moser and Guillaume Oldenhove

Abstract

Tissue hypoxia can occur in physiological and pathological conditions. When O2 availability decreases, the transcription factor hypoxia-inducible factor (HIF)-1α is stabilized and regulates cellular adaptation to hypoxia. The objective of this study was to test whether HIF-1α regulates T cell fate and to define the molecular mechanisms of this control. Our data demonstrate that Th1 cells lose their capacity to produce IFN-γ when cultured under hypoxia. HIF-1α-/- Th1 cells were insensitive to hypoxia, underlining a critical role for HIF-1α. Our results point to a role for IL-10, as suggested by the increased IL-10 expression at low O2 levels and the unchanged IFN-γ production by IL-10-deficient Th1 cells stimulated in hypoxic conditions. Accordingly, STAT3 phosphorylation is increased in Th1 cells under hypoxia, leading to enhanced HIF-1α transcription, which, in turn, may inhibit suppressor of cytokine signaling 3 transcription. This positive-feedback loop reinforces STAT3 activation and downregulates Th1 responses that may cause collateral damage to the host.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Topics: Sciences bio-médicales et agricoles
Year: 2015
DOI identifier: 10.4049/jimmunol.1402552
OAI identifier: oai:dipot.ulb.ac.be:2013/217555
Provided by: DI-fusion
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