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Possible role of the ‘IDO‐AhR axis’ in maternal‐foetal tolerance
Author(s) -
Hao Kehong,
Zhou Qian,
Chen Wen,
Jia Wenwen,
Zheng Jing,
Kang Jiuhong,
Wang Kai,
Duan Tony
Publication year - 2013
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10023
Subject(s) - immune tolerance , kynurenine , immunologic tolerance , immunology , aryl hydrocarbon receptor , placenta , immune system , biology , indoleamine 2,3 dioxygenase , peripheral tolerance , pregnancy , fetus , microbiology and biotechnology , genetics , tryptophan , transcription factor , gene , amino acid
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 (T reg ) 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 T reg 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 T reg 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.