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促进结肠细胞中 Foxp3 的表达 PD-L1 介导的 PI3K-Akt-mTOR 信号通路的抑制作用。

Promotes Foxp3 Expression in Colon Cells PD-L1-Mediated Inhibition of the PI3K-Akt-mTOR Signaling Pathway.

机构信息

Gastroenterology department, ShengJing Hospital of China Medical University, Shenyang, China.

出版信息

Front Immunol. 2022 Jul 4;13:871705. doi: 10.3389/fimmu.2022.871705. eCollection 2022.

DOI:10.3389/fimmu.2022.871705
PMID:35860248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9289111/
Abstract

AIM

Our objective was to investigate whether Bifidobacterium infantis inhibits PI3K-Akt-mTOR signaling and upregulates Foxp3 expression through PD-L1 and to explore the possible mechanism of action of B. infantis in cellular immunosuppression.

METHOD

The effects of B. infantis supernatant on PD-L1, PD-1, Foxp3, and the PI3K-Akt-mTOR signaling pathway were observed by culturing HCT-116 cells. Simultaneously, the effects of blocking PD-L1 on PD-1, on Foxp3 protein and mRNA, and on the PI3K-Akt-mTOR signaling pathway protein were observed.

RESULTS

B. infantis supernatant was able to upregulate the protein and mRNA expression of PD-L1 and Foxp3 and downregulate the phosphorylated protein expression of PI3K, Akt, and mTOR (P < 0.05); however, for PI3K, Akt, and mTOR, there was no change in the total protein expression. After the blocking of PD-L1, the stimulatory effect of B. infantis supernatant on Foxp3 and the inhibitory effect on the phosphorylated protein expression of PI3K, Akt, and mTOR were weakened.

CONCLUSION

B. infantis may inhibit the PI3K-Akt-mTOR signaling pathway and promote the expression of Foxp3 through PD-L1, which may be a target which B. infantis exerts its immunosuppressive effect.

摘要

目的

本研究旨在探讨婴儿双歧杆菌是否通过 PD-L1 抑制 PI3K-Akt-mTOR 信号通路并上调 Foxp3 表达,并探索婴儿双歧杆菌在细胞免疫抑制中的可能作用机制。

方法

通过培养 HCT-116 细胞,观察婴儿双歧杆菌上清液对 PD-L1、PD-1、Foxp3 和 PI3K-Akt-mTOR 信号通路的影响。同时,观察阻断 PD-L1 对 PD-1、Foxp3 蛋白和 mRNA 以及 PI3K-Akt-mTOR 信号通路蛋白的影响。

结果

婴儿双歧杆菌上清液能上调 PD-L1 和 Foxp3 的蛋白和 mRNA 表达,并下调 PI3K、Akt 和 mTOR 的磷酸化蛋白表达(P<0.05);然而,对于 PI3K、Akt 和 mTOR,总蛋白表达没有变化。阻断 PD-L1 后,婴儿双歧杆菌上清液对 Foxp3 的刺激作用以及对 PI3K、Akt 和 mTOR 磷酸化蛋白表达的抑制作用减弱。

结论

婴儿双歧杆菌可能通过 PD-L1 抑制 PI3K-Akt-mTOR 信号通路并促进 Foxp3 的表达,这可能是婴儿双歧杆菌发挥免疫抑制作用的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/8e32194d4ddc/fimmu-13-871705-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/eb079c776766/fimmu-13-871705-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/bd1868f53a85/fimmu-13-871705-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/eda88758fe94/fimmu-13-871705-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/6ab2b1dff344/fimmu-13-871705-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/ee85a63b4560/fimmu-13-871705-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/8e32194d4ddc/fimmu-13-871705-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/eb079c776766/fimmu-13-871705-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/bd1868f53a85/fimmu-13-871705-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/eda88758fe94/fimmu-13-871705-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/6ab2b1dff344/fimmu-13-871705-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/ee85a63b4560/fimmu-13-871705-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ac/9289111/8e32194d4ddc/fimmu-13-871705-g006.jpg

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