Regulatory T Cells Improved the Anti-cirrhosis Activity of Human Amniotic Mesenchymal Stem Cell in the Liver by Regulating the TGF-β-Indoleamine 2,3-Dioxygenase Signaling.
Regulatory T Cells Improved the Anti-cirrhosis Activity of Human Amniotic Mesenchymal Stem Cell in the Liver by Regulating the TGF-β-Indoleamine 2,3-Dioxygenase Signaling.
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调节性 T 细胞通过调节 TGF-β-吲哚胺 2,3-双加氧酶信号传导改善肝脏中人羊膜间充质干细胞的抗肝硬化活性
DOI：
10.3389/fcell.2021.737825
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xia Y
中科院分区：
文献类型：
--
作者：
Deng Z;Zhou J;Mu X;Gu J;Li X;Shao Q;Li J;Yang C;Han G;Zhao J;Xia Y
肝纤维化是慢性肝病的一个进展阶段，而目前的治疗方法无法有效治愈或调节肝硬化。人羊膜间充质基质细胞（hAMSC）具有多种疾病的免疫调节和组织修复能力。调节性 T 细胞 (Treg) 已被证明具有降低免疫细胞活性的功能。我们发现，与单独 hAMSC 或 Treg 组相比，联合输注 hAMSC 和 Treg 可以预防轻度肝纤维化。体外研究表明，添加Treg或Treg上清可以提高hAMSC的肝细胞生长因子（HGF）分泌和细胞分化能力。 TGF-β的减少显着降低了hAMSC的HGF分泌和分化。在培养物中添加多种信号中和剂以进一步了解其机制，结果表明吲哚胺2,3-双加氧酶（IDO）的抑制剂1-MT参与TGF-β调节hAMSC的作用。 TGF-β或IDO信号传导的耗竭成功消除了Treg在体外和体内改善hAMSC功能的作用。最后，我们的结果表明，Treg 通过调节 TGF-β-IDO 信号传导改善了 hAMSC 的功能，hAMSC 和 Treg 的共输注为治疗肝硬化提供了一种有前景的方法。
Liver fibrosis is a progression stage of chronic liver disease, while current therapies cannot cure or attune cirrhosis effectively. Human amniotic mesenchymal stromal cell (hAMSC) presented immunoregulatory and tissue repairability of multiple illnesses. Regulatory T cells (Treg) had been proved to be functional in reducing immune cell activity. We showed that co-infusion of hAMSC and Treg prevented mild liver fibrosis comparing with hAMSC or Treg alone group. In vitro study indicated that the addition of Treg or the supernatant of Treg improved the hepatocyte growth factor (HGF) secreting and cell differentiation ability of hAMSC. Reduction of TGF-β significantly decreased the HGF secreting and differentiation of hAMSC. Multiple signal neutralizers were added to the culture to understand further the mechanism, which showed that 1-MT, the suppressor of Indoleamine 2,3-dioxygenase (IDO), was involved in the effect of TGF-β in regulating hAMSC. Depletion of TGF-β or IDO signaling successfully abolished the effect of Treg in improving hAMSC’s function both in vitro and vivo. Finally, our result indicated that Treg improved the function of hAMSC by regulating the TGF-β-IDO signaling and co-infusion of hAMSC and Treg provided a promising approach for treating liver cirrhosis.
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间充质干细胞治疗肝纤维化。
DOI：
10.3904/kjim.2015.30.5.580
发表时间：
2015-09
期刊：
The Korean journal of internal medicine
影响因子：
--
作者：
Eom YW;Shim KY;Baik SK
通讯作者：
Baik SK
影响因子：
16.8
作者：
Munn DH;Mellor AL
通讯作者：
Mellor AL
影响因子：
12.8
作者：
Kim, Myung-Deok;Kim, Sung-Soo;Cha, Hyun-Young;Jang, Seung-Hun;Chang, Da-Young;Kim, Wookhwan;Suh-Kim, Haeyoung;Lee, Jae-Ho
通讯作者：
Lee, Jae-Ho
影响因子：
4.4
作者：
Fallarino, F;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
16.6
作者：
Salmon, Richard M.;Guo, Jingxu;Li, Wei
通讯作者：
Li, Wei