Abstract
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.
Footnotes
This work was supported by Grant 1UL1RR025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health (to J.D.M.), National Institute on Environmental Health Sciences Grant R37ES005703 (to C.A.B.), National Cancer Institute Grant P30CA014520 (to C.A.B.), an American Society of Transplant Surgeons-Astellas Faculty Development Award (to J.D.M.), National Institute of Allergy and Infectious Diseases Grant RO1AI066219 (to W.J.B.), and National Institutes of Health Training Grant T32ES007015-32 (to B.P.J.).
The online version of this article contains supplemental material.
Abbreviations used in this paper:
- AHR
- aryl hydrocarbon receptor
- BMDC
- bone marrow-derived dendritic cell
- DC
- dendritic cell
- DRE
- dioxin-responsive element
- FICZ
- 6-formylindolo[3,2-b]carbazole
- nt
- not tested
- pDC
- plasmacytoid dendritic cell
- qPCR
- quantitative PCR
- TCDD
- 2,3,7,8-tetrachlorodibenzo-p-dioxin
- Treg
- regulatory T cell
- WT
- wild-type.
- Received November 13, 2009.
- Accepted July 8, 2010.
- Copyright © 2010 by The American Association of Immunologists, Inc.
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