Related Experiment Video

Updated: Jun 10, 2026

Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures
10:38

Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures

Published on: May 9, 2020

An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells

Joshua D Mezrich1, John H Fechner, Xiaoji Zhang

  • 1Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375, USA. mezrich@surgery.wisc.edu

Journal of Immunology (Baltimore, Md. : 1950)
|August 20, 2010
PubMed

Insights

Kynurenine activates the aryl hydrocarbon receptor (AHR), driving T cell differentiation into regulatory T cells (Tregs). This pathway highlights the AHR’s crucial role in immune cell development and the IDO-Treg connection.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The aryl hydrocarbon receptor (AHR) is known for its role in dioxin-induced immunosuppression.
  • Emerging evidence suggests AHR involvement in T cell differentiation, specifically towards regulatory T cells (Tregs) and Th17 cells.

Purpose of the Study:

  • To investigate the role of kynurenine, a tryptophan metabolite, in activating the AHR.
  • To determine if AHR activation by kynurenine drives Treg generation.
  • To explore the interplay between TGF-beta, AHR, and Treg development.

Main Methods:

  • Treatment of mouse T cells with kynurenine.
  • Assessment of AHR activation.
  • Analysis of Treg (FoxP3+) differentiation.
  • Investigation of TGF-beta's influence on AHR expression and Treg generation.

Main Results:

  • Kynurenine was demonstrated to activate the AHR.
  • AHR activation by kynurenine was shown to be essential for Treg generation.
  • TGF-beta's role in Treg generation was investigated in the context of AHR upregulation.

Conclusions:

  • Kynurenine activates the AHR, promoting Treg differentiation.
  • The study elucidates the IDO-kynurenine-AHR axis in Treg generation.
  • AHR is confirmed as a key mediator in T cell differentiation pathways.

More Related Videos

Generation of Human Chimeric Antigen Receptor Regulatory T Cells10:29

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells14:23

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...