Cited by 518Cancer, Hypoxia, and MetabolismAdenosine and Purinergic SignalingImmune cells in cancer

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Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors

Sitkovsky, Michail, Lukashev, Dmitriy·2005·Nature Reviews Immunology

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Abstract

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.

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Authors: Sitkovsky, M., & Lukashev, D.
Affiliations: Northeastern University (US)
Corresponding author: Sitkovsky, Michail
ORCID: Sitkovsky, Michail
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2005-08-19
Volume: 5
Issue: 9
Pages: 712-721
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri1685
OpenAlex: W2089916504
Semantic Scholar: 86ac33e3809727856e079e987663bd86cf83fd9d
Cited by: 518
References: 126
Citations by year: 2026: 7 · 2025: 16 · 2024: 17 · 2023: 15 · 2022: 14 · 2021: 37 · 2020: 29 · 2019: 18 · 2018: 23 · 2017: 23 · 2016: 21 · 2015: 17 · 2014: 32 · 2013: 38 · 2012: 41
FWCI: 2.31
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: hypoxia, tissue oxygen tension, HIF-1α, adenosine receptors, T cell metabolism, glycolysis, inflammation, innate immune cells, immune cell regulation, energy metabolism
MeSH terms: Animals, T-Lymphocytes, Helper-Inducer, Humans, Oxygen, Partial Pressure, Transcription Factors, Receptors, Purinergic P1, Hypoxia-Inducible Factor 1, alpha Subunit

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Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors

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