AN INTERACTION BETWEEN KYNURENINE AND THE ARYL HYDROCARBON RECEPTOR CAN GENERATE REGULATORY T CELLS,
By J. Mezrich, J. Fechner, Xiaoji Zhang, Brian P Johnson, W. Burlingham, Christopher A. Bradfield. Journal of Immunology, 2010
1,521 citations recorded by the source corpus.
The aryl hydrocarbon receptor (AHR) has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3+ regulatory T cells (Tregs) versus Th17 cells. In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent Treg generation. We additionally investigate the dependence of TGF-β on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells postexposure to TGF-β. These results shed light on the relationship of IDO to the generation of Tregs, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.
Subfields: Behavioral Neuroscience, Biological Psychiatry, Endocrine and Autonomic Systems
View Paper: https://www.semanticscholar.org/paper/e34d7e7e3c7988aa6e99509b1b28b46f9b1ab7b9
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Citations in the corpus
- Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. (2012, background): “org Cancer Res; 72(21) November 1, 2012 5437”
- IDO in the Tumor Microenvironment: Inflammation, Counter-regulation and Tolerance (2016, positive): “The AhR can promote Treg cell differentiation [29, 30], and can also bias dendritic cells (DCs) and macrophages toward an immunosuppressive phenotype [6, 31-33].”
- Metabolic Interactions in the Tumor Microenvironment (2017, background): “Activation of AHR signaling in CD4+ T cells primes their differentiation into the immunosuppressive T regulatory fate [82] and negatively regulates dendritic cell immunogenicity [83].”
- Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism (2013, background): “Members of the DMC participate in immunoactive tryptophan catabolism IDO1 is induced during inflammation and is thought to actively regulate immune activation by its numerous effects on T cells, including inhibition of IL-17 secretion and induction of FoxP3-expressing regulatory T cells (Tregs) (45)”
- Tolerogenic dendritic cells (2016, background): “Concomitantly, AhR activation boosts the ability of DCs to promote the differentiation and expansion of FoxP3 Tregs through the production of kynurenins and RA [55, 94, 95].”
- The secretion profile of mesenchymal stem cells and potential applications in treating human diseases (2022, background): “As reported, KYN induces FOXP3 Tregs in an aryl hydrocarbon receptor (AhR)-dependent manner, the binding of kynurenine to the AHR could be further potentiated by TGF-β.(194) In human MSCs, we have found that kynurenic acid (KYNA), which is another IDO-derived metabolite with little cytotoxicity and ”
- Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. (2013, positive): “, 2011) and promotes Treg cell development (Fallarino et al., 2006; Mezrich et al., 2010).”