Thymocyte development in Ah-receptor-deficient mice is refractory to TCDD-inducible changes
Thymocyte development in Ah-receptor-deficient mice is refractory to TCDD-inducible changes
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DOI：
10.1016/s0192-0561(99)00053-3
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发表时间：
1999-12-01
期刊：
影响因子：
--
通讯作者：
Esser, C
中科院分区：
文献类型：
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作者：
Hundeiker, C;Pineau, T;Esser, C
芳烃受体（AhR）是一种配体激活的转录因子，在组织中有差异分布，在胸腺上皮中含量丰富。激活的AhR可以诱导一系列基因的转录，包括细胞生长和分化的基因。AhR的生理功能及其推定的天然配体都是未知的。2，3，7，8-四氯二苯并-对-二恶英（TCDD）是AhR的高亲和力激活剂，并且似乎是TCDD的大多数多重毒性效应所必需的。即使是低剂量的TCDD也会激活AhR，导致全身免疫抑制和胸腺发育不全。接触TCDD会干扰胸腺细胞的发育;例如，它会降低极不成熟（CD 4（-）CD 8（-）和CD 4（-）CD 8（+）HSA（+））胸腺细胞的增殖率，导致极不成熟细胞优先迁移，并使胸腺细胞亚群向成熟的CD 4（-）CD 8（+）α β TCR高胸腺细胞分化。如图所示，在AhR缺陷小鼠的胎儿胸腺中，由CD 4和CD 8表面标志物定义的胸腺细胞分化动力学与AhR（+/+）C57 BL/6小鼠相当。此外，细胞迁移特征与AhR（+/+）小鼠相似。这些参数在AhR（-/-）小鼠中对TCDD暴露不敏感，但在C57 BL/6小鼠中则不然。然而，在AhR缺陷小鼠妊娠第15天，更多的CD 4（-）CD 8（-）未成熟细胞携带大量的α β-T细胞受体。此外，胎儿胸腺细胞的数量显着较低，相比，菌株C57 BL/6。因此，AhR是TCDD的胸腺毒性作用的介质。由爱思唯尔科技有限公司出版。保留所有权利。
The arylhydrocarbon receptor (AhR), a ligand-activated transcription factor, is differentially distributed in tissues and abundant in the thymus epithelium. The activated AhR can induce the transcription of an array of genes, including genes of cell growth and differentiation. Neither the physiological function of the AhR nor its putative natural ligand is known. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a xenobiotic high-affinity activator of the AhR, and appears to be essential for most of the multifold toxic effects of TCDD. Activation of the AhR by even low doses of TCDD results in general immunosuppression and thymus hypoplasia. TCDD exposure interferes with thymocyte development; for instance, it reduces the proliferation rate of the very immature (CD4(-)CD8(-) and CD4(-)CD8(+)HSA(+)) thymocytes, leads to preferential emigration of very immature cells, and drastically skews the differentiation of thymocyte subpopulations towards mature CD4(-)CD8(+) alpha beta TCRhigh thymocytes. As shown here, in fetal thymi of AhR-deficient mice, thymocyte differentiation kinetics as defined by CD4 and CD8 surface markers, was comparable to AhR(+/+) C57BL/6 mice. Also, the cell emigration characteristics were similar to AhR(+/+) mice. These parameters were refractory to TCDD exposure in the AhR(-/-) mice, but not in the C57BL/6 mice. However, in AhR deficient mice at gestation day 15 more CD4(-)CD8(-) immature cells bore high amounts of the (alpha beta-T-cell receptor. Also, fetal thymocyte numbers were significantly lower, as compared to strain C57BL/6. Thus, the AhR is the mediator of thymotoxic effects of TCDD. Published by Elsevier Science Ltd. All rights reserved.