Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors.
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.
Sitkovsky
Michail
M
New England Inflammation and Tissue Protection Institute, Northeastern University, 360 Huntington Avenue, 134MU, Boston, Massachusetts 02115, USA. m.sitkovsky@neu.edu
Lukashev
Dmitriy
D
D000818:Animals; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D010313:Partial Pressure; D018047:Receptors, Purinergic P1 / Q000378:metabolism / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018047:Receptors, Purinergic P1; D014157:Transcription Factors; D010100:Oxygen