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Hum Immunol. 2008 Jul;69(7):421-5. doi: 10.1016/j.humimm.2008.05.004. Epub 2008 Jun 11.

Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1alpha in activated human T lymphocytes.

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  • 1New England Inflammation and Tissue Protection Institute, Northeastern University, Boston, MA, USA.


Hypoxia-inducible factor-1alpha (HIF-1alpha) is critical not only in the regulation of oxygen homeostasis but also in the regulation of innate and adaptive immune systems. We previously reported that T-cell receptor-mediated activation of T cells in mice leads to the expression of an alternative isoform of HIF-1alpha that inhibits activated T cells in a delayed negative feed-back manner. In this paper, we describe a novel mRNA isoform of human HIF-1alpha that is upregulated in peripheral T lymphocytes after T-cell receptor stimulation. This activation- inducible isoform is expressed using the alternative first exon I.3, and it encodes a protein that is 24 amino acids longer than the ubiquitous HIF-1alpha isoform. This mRNA isoform I.3 of HIF-1alpha is expressed in a tissue-specific manner with the highest expression found in peripheral blood leukocytes and the thymus.

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