Wang Xiaoyan, Yuan Ting, Yin Nannan, Ma Xiaofei, Yang Yaping, Yang Jing, Shaukat Aftab, Deng Ganzhen
Department of Clinical Veterinary Medicine, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
College of Animal Science and Technology, Chongqing Three Gorges Vocational College, Chongqing 404155, P.R. China.
Exp Ther Med. 2021 Jun;21(6):594. doi: 10.3892/etm.2021.10026. Epub 2021 Apr 8.
IFN-τ is a pregnancy recognition factor that regulates embryo implantation in ruminants. IFN-τ has been suggested to be involved in the expression of microRNA (miRNA/miR) and bovine leukocyte antigen (BoLA), which is an analog of the human major histocompatibility complex class I. However, little is known about whether the miRNAs are involved in the expression of BoLA in ruminants. The present study firstly verified that bta-miR-204 was downregulated and that BoLA was upregulated in the uterine tissues of dairy cows during early pregnancy. Subsequently, luciferase reporter assays, reverse transcription-quantitative PCR and western blot analysis were used to validate BoLA as the target gene of bta-miR-204. Moreover, BoLA was markedly upregulated and bta-miR-204 was downregulated in bovine endometrial epithelial cells (bEECs) treated with IFN-τ. In addition, the results indicated that when the expression level of BoLA was increased by IFN-τ, the expression level of programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) was also increased. Furthermore, when BoLA was silenced in bEECs by small interfering RNA, the expression of PD-L1 and PD-L2 was not affected by IFN-τ. The expression level of PD-L1 and PD-L2 was also increased in the uterine tissues of pregnant dairy cattle. In conclusion, IFN-τ may function by suppressing the expression of bta-miR-204 to increase the expression of BoLA during the embryo implantation period in cattle. IFN-τ may induce PD-L1 and PD-L2 transcription by regulating BoLA, which may influence the T cell immune response, thereby regulating pregnant cattle immunization.
干扰素-τ是一种调节反刍动物胚胎着床的妊娠识别因子。有人提出干扰素-τ参与微小RNA（miRNA/miR）和牛白细胞抗原（BoLA）的表达，BoLA是人类主要组织相容性复合体I类的类似物。然而，关于miRNA是否参与反刍动物BoLA的表达，人们了解甚少。本研究首先证实，在奶牛妊娠早期，子宫组织中bta-miR-204表达下调，而BoLA表达上调。随后，采用荧光素酶报告基因检测、逆转录定量PCR和蛋白质印迹分析来验证BoLA是bta-miR-204的靶基因。此外，在用干扰素-τ处理的牛子宫内膜上皮细胞（bEECs）中，BoLA明显上调，而bta-miR-204下调。另外，结果表明，当干扰素-τ使BoLA表达水平升高时，程序性死亡配体1（PD-L1）和程序性死亡配体2（PD-L2）的表达水平也升高。此外，当通过小干扰RNA使bEECs中的BoLA沉默时，PD-L1和PD-L2的表达不受干扰素-τ的影响。妊娠奶牛子宫组织中PD-L1和PD-L2的表达水平也升高。总之，在牛的胚胎着床期，干扰素-τ可能通过抑制bta-miR-204的表达来增加BoLA的表达发挥作用。干扰素-τ可能通过调节BoLA诱导PD-L1和PD-L2转录，这可能影响T细胞免疫反应，从而调节妊娠母牛的免疫。
