Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors

Nat Rev Immunol. 2005 Sep;5(9):712-21. doi: 10.1038/nri1685.


Immune cells are often exposed to low oxygen tensions, which markedly affect cellular metabolism. We describe how activated T cells adapt to the changing energy supplies in hypoxic areas of inflamed tissues by using hypoxia-inducible factor 1 (HIF1) to switch to glycolysis as the main source of energy and by signalling through extracellular-adenosine receptors. This hypoxic regulation might alter the balance between T helper 1 cells and T helper 2 cells and might alter the activities of cells of the innate immune system, thereby qualitatively and quantitatively affecting immune responses. This regulatory mechanism should be taken into account in the design and interpretation of in vitro and in vivo studies of immune-cell effector functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen / metabolism
  • Oxygen / physiology*
  • Partial Pressure
  • Receptors, Purinergic P1 / metabolism
  • Receptors, Purinergic P1 / physiology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Helper-Inducer / physiology
  • Transcription Factors / physiology*


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, Purinergic P1
  • Transcription Factors
  • Oxygen