Possible role of the 'IDO-AhR axis' in maternal-foetal tolerance
Possible role of the 'IDO-AhR axis' in maternal-foetal tolerance
复制标题
DOI：
10.1002/cbin.10023
复制
发表时间：
2013-02-01
影响因子：
3.9
通讯作者：
Duan, Tony
中科院分区：
文献类型：
--
作者：
Hao, Kehong;Zhou, Qian;Duan, Tony
在母胎界面诱导和维持免疫耐受是成功妊娠所必需的。对于这种耐受性的机制，最被接受的假设是妊娠诱导的胎儿抗原特异性母体T调节（T-reg）细胞介导母体对胎儿的耐受性。芳香烃受体（AhR）在胎盘中高度表达，在女性生殖生物学和免疫学中被广泛研究。在某些自身免疫性疾病中，AhR的激活可以通过控制T-reg细胞的分化来促进免疫耐受。然而，耐受性的具体机制知之甚少。吲哚胺2，3-双加氧酶（IDO）是人胎盘滋养层细胞色氨酸催化的起始酶和限速酶。IDO产生犬尿氨酸，一种直接激活AhR的内源性AhR配体，并被认为是在母胎界面建立和维持免疫耐受的关键。我们提出犬尿氨酸激活AhR，导致AhR依赖性T-reg细胞的产生，这反过来又严格调节胎儿-母体界面的免疫耐受。必须对这一假设进行检验，这一假设的证明可能为治疗不孕症和因胎儿-母体界面免疫耐受性不足而导致的其他不良妊娠结果提供潜在的治疗靶点。
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.