New insights into the role of AHR in IDO1-induced immunosuppression
(2022)
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- Abstract
- Tumor cells use different mechanisms to avoid immune recognition. One of these is the induction of the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3 dioxygenase (TDO) responsible for catabolizing the essential amino acid tryptophan into kynurenine. The aim of this work was to elucidate the pathway that translates these metabolic changes into T-lymphocyte malfunction within the tumor microenvironment. We show that through the aryl hydrocarbon receptor (AHR), CD4+ T lymphocytes from DBA/2 mice, differentiate significantly more into immunosuppressive regulatory T cells (Treg) when cultured in absence of tryptophan. More importantly, we found that under tryptophan-depleted conditions, AHR was significantly upregulated rendering it more sensitive to ligands such as kynurenine. Overall, our findings provide new insights into the respective role of tryptophan depletion and kynurenine production in IDO1/TDO-mediated immunosuppression.
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Citations
Solvay, M. (2022). New insights into the role of AHR in IDO1-induced immunosuppression. https://hdl.handle.net/2078.5/101749