Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes
- PMID: 17015677
- DOI: 10.4049/jimmunol.177.8.4962
Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes
Abstract
To evaluate the role of hypoxia-inducible factor 1alpha (HIF-1alpha) and its TCR activation-inducible short isoform I.1 in T cell functions, we genetically engineered unique mice with: 1) knockout of I.1 isoform of HIF-1alpha; 2) T cell-targeted HIF-1alpha knockdown; and 3) chimeric mice with HIF-1alpha gene deletion in T and B lymphocytes. In all three types of mice, the HIF-1alpha-deficient T lymphocytes, which were TCR-activated in vitro, produced more proinflammatory cytokines compared with HIF-1alpha-expressing control T cells. Surprisingly, deletion of the I.1 isoform, which represents < 30% of total HIF-1alpha mRNA in activated T cells, was sufficient to markedly enhance TCR-triggered cytokine secretion. These data suggest that HIF-1alpha not only plays a critical role in oxygen homeostasis but also may serve as a negative regulator of T cells.
Similar articles
-
Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1 alpha in activated T lymphocytes.J Biol Chem. 2001 Dec 28;276(52):48754-63. doi: 10.1074/jbc.M104782200. Epub 2001 Oct 15. J Biol Chem. 2001. PMID: 11602577
-
Sphingosine-1-phosphate reduces CD4+ T-cell activation in type 1 diabetes through regulation of hypoxia-inducible factor short isoform I.1 and CD69.Diabetes. 2008 Feb;57(2):484-93. doi: 10.2337/db07-0855. Epub 2007 Nov 14. Diabetes. 2008. PMID: 18003758
-
Macrophage oxygen sensing modulates antigen presentation and phagocytic functions involving IFN-gamma production through the HIF-1 alpha transcription factor.J Immunol. 2009 Mar 1;182(5):3155-64. doi: 10.4049/jimmunol.0801710. J Immunol. 2009. PMID: 19234213
-
Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells.Biol Chem. 2013 Apr;394(4):495-505. doi: 10.1515/hsz-2012-0320. Biol Chem. 2013. PMID: 23362200 Review.
-
Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery:inflammatory responses of hypoxia-inducible factor 1α (HIF-1α) in T cells observed in development of vascular remodeling.J Pharmacol Sci. 2011;115(4):433-9. doi: 10.1254/jphs.10r22fm. Epub 2011 Mar 16. J Pharmacol Sci. 2011. PMID: 21422726 Review.
Cited by
-
Phenotypic switch of CD8(+) T cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells.Eur J Immunol. 2015 Aug;45(8):2263-75. doi: 10.1002/eji.201445284. Epub 2015 May 26. Eur J Immunol. 2015. PMID: 25929785 Free PMC article.
-
Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma.J Transl Med. 2016 Apr 5;14:85. doi: 10.1186/s12967-016-0828-6. J Transl Med. 2016. PMID: 27044404 Free PMC article. Review.
-
Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?Purinergic Signal. 2013 Jun;9(2):145-65. doi: 10.1007/s11302-012-9349-9. Epub 2012 Dec 28. Purinergic Signal. 2013. PMID: 23271562 Free PMC article. Review.
-
T cell exhaustion in malignant gliomas.Trends Cancer. 2023 Apr;9(4):270-292. doi: 10.1016/j.trecan.2022.12.008. Epub 2023 Jan 19. Trends Cancer. 2023. PMID: 36681605 Free PMC article. Review.
-
Hypoxia inducible factor (HIF) function in innate immunity and infection.J Mol Med (Berl). 2007 Dec;85(12):1339-46. doi: 10.1007/s00109-007-0282-2. Epub 2007 Nov 21. J Mol Med (Berl). 2007. PMID: 18030436 Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
