The transcription factor HIF1α controls expression of the cytokine IL-22 in CD4 T cells

Abstract

IL-22 is expressed by activated lymphocytes and is important in modulation of tissue responses during inflammation. The cytokine induces proliferative and anti-apoptotic pathways in epithelial cells allowing enhanced cell survival. This can have positive effects, such as in the maintenance of epithelial barriers in the gastrointestinal tract, but also negative effects, such as contributing to colorectal tumorigenesis. As IL-22 can be dual-natured, we hypothesized that its biological activity should be tightly regulated in order to limit IL-22 expression to the sites of inflammation. One such environmental cue could be low oxygen, which often accompanies inflammation. We show that in CD4 T cells IL-22 expression is upregulated in hypoxia, and this upregulation is dependent on the transcription factor hypoxia-inducible factor 1α (HIF1α). This finding has implications on the regulation of Il22 gene expression and the cytokine’s presence in different inflammatory environments.