An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells

Journal of Immunology - Tập 185 Số 6 - Trang 3190-3198 - 2010
Joshua D. Mezrich1, John H. Fechner2, Xiaoji Zhang2, Brian P. Johnson3, William J. Burlingham2, Christopher A. Bradfield3
1Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375, USA.
2*Division of Transplantation, Department of Surgery and
3†McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

Tóm tắt

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.

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