Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors
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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HIF1A is a transcription factor that performs an essential role in cellular responses to hypoxia, is involved in regulation of macrophage migration, and modulates metabolism of immune cells exposed to low oxygen tensions in hypoxic areas of inflamed tissues.
“Co-expressed with Mac-1 components, the hypoxia-inducible factor 1 (HIF1A) is a well characterized transcription factor that performs an essential role in cellular responses to hypoxia. HIF1A is also involved in the regulation of macrophage migration, and modulates the metabolism of immune cells exposed to low oxygen tensions in hypoxic areas of inflamed tissues [30].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [30]
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- Authors
- Sitkovsky, M., & Lukashev, D.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Sitkovsky, Michail
- ORCID
- Sitkovsky, Michail
- Venue
- Nature Reviews Immunology
- Published
- 2005-08-19
- Volume
- 5
- Issue
- 9
- Pages
- 712-721
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- 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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