Cytochrome P450 26A1 modulates uterine dendritic cells in mice early pregnancy
Cytochrome P450 26A1 modulates uterine dendritic cells in mice early pregnancy
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细胞色素 P450 26A1 调节小鼠妊娠早期子宫树突状细胞
DOI：
10.1111/jcmm.14423
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发表时间：
2019-08-01
影响因子：
5.3
通讯作者：
Peng, Jing-Pian
中科院分区：
文献类型：
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作者：
Gu, Ai-Qin;Li, Dan-Dan;Peng, Jing-Pian
细胞色素P450 26 A1（CYP 26 A1）在小鼠围着床期发挥重要作用。抑制其表达或功能会导致妊娠失败。然而，人们对CYP 26 A1的潜在机制知之甚少，特别是CYP 26 A1与免疫细胞之间的关系。本研究采用Cyp 26 a1特异性反义寡核苷酸（Cyp 26 a1-MO）敲除小鼠模型和pCR3.1-Cyp 26 a1疫苗小鼠模型，发现经处理的小鼠子宫CD 45（+）CD 11 c（+）MHCII（lo-hi）F4/80（-）树突状细胞（DCs）数量显著减少。与对照组相比，治疗组子宫DCs中成熟DCs（CD 86（hi））的百分比明显降低，未成熟DCs（CD 86（lo））的百分比明显升高。进一步的实验发现，治疗组小鼠子宫中与DC发育相关的转录因子ID 2和DC成熟标记分子CD 86均显著降低。在体外，Cyp 26 a1-MO处理的骨髓来源的DC中的ID 2和CD 86也降低。这些结果为CYP 26 A1可能通过调节子宫DCs的分化和成熟而影响胚胎着床提供了新的信息。
Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri-implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1-specific antisense morpholigos (Cyp26a1-MO) knockdown mice model and pCR3.1-Cyp26a1 vaccine mice model, we found that the number of uterine CD45(+)CD11c(+)MHCII(lo-hi)F4/80(-) dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86(hi)) was obviously lower and the percentage of immature DCs (CD86(lo)) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow-derived DCs under Cyp26a1-MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.