Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200040, P.R. China.
Cell Biol Int. 2013 Feb;37(2):105-8. doi: 10.1002/cbin.10023. Epub 2013 Jan 2.
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.
在母体-胎儿界面诱导和维持免疫耐受对于成功妊娠是必要的。最被接受的关于这种耐受机制的假说认为，妊娠诱导的胎儿抗原特异性母体调节性 T 细胞（Treg）介导母体对胎儿的耐受。芳香烃受体（AhR）在胎盘组织中高度表达，在女性生殖生物学和免疫学中得到广泛研究。在某些自身免疫性疾病中，AhR 的激活可以通过控制 Treg 细胞的分化来促进免疫耐受。然而，耐受的具体机制尚不清楚。色氨酸分解代谢的初始限速酶吲哚胺 2,3-双加氧酶（IDO）在人胎盘滋养层细胞中表达。IDO 产生犬尿氨酸，一种内源性 AhR 配体，可直接激活 AhR，并被认为是在母体-胎儿界面建立和维持免疫耐受的核心。我们提出，犬尿氨酸激活 AhR，导致 AhR 依赖性 Treg 细胞的产生，进而严格调节母体-胎儿界面的免疫耐受。这一假说必须经过验证，这一假说的证明可能为治疗因母体-胎儿界面免疫耐受不足而导致的不孕和其他不良妊娠结局提供潜在的治疗靶点。
