Possible role of the ‘IDO-AhR axis’ in maternal-foetal tolerance

Authors

  • Kehong Hao,

    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
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  • Qian Zhou,

    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
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  • Wen Chen,

    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
    2. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China
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  • Wenwen Jia,

    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
    2. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China
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  • Jing Zheng,

    1. Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA
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  • Jiuhong Kang,

    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
    2. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China
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  • Kai Wang,

    Corresponding author
    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
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  • Tony Duan

    Corresponding author
    1. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
    2. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China
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  • Kehong Hao and Qian Zhou contributed equally to this work.

Abstract

The induction and maintenance of immunologic tolerance at the feto-maternal interface is necessary for a successful pregnancy. The most accepted hypothesis for the mechanism underlying this tolerance is that pregnancy-induced foetal antigen-specific maternal T regulatory (Treg) cells mediate maternal tolerance to the foetus. The aryl hydrocarbon receptor (AhR), which is highly expressed in the placenta, is widely studied in female reproductive biology and immunology. Activation of AhR can promote immune tolerance by controlling the differentiation of Treg cells in some autoimmune disorders. However, the specific mechanisms underlying tolerance are poorly understood. Indoleamine 2,3-dioxygenase (IDO) is the initial and rate-limiting enzyme of tryptophan catabolism in human placental trophoblasts. IDO produces kynurenine, an endogenous AhR ligand that directly activates AhR and is proposed to be central to the establishment and maintenance of immunologic tolerance at the maternal-foetal interface. We propose that kynurenine activates AhR, leading to the AhR-dependent Treg cells generation, which in turn critically regulates immunological tolerance at the feto-maternal interface. This hypothesis must be tested and the proof of this hypothesis may provide a potential therapeutic target for the treatment of infertility and other adverse pregnancy outcomes resulted from inadequate immunological tolerance at the feto-maternal interface.

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