Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis.
Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis.
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吲哚胺 2,3-双加氧酶 1 限制肝脏炎症细胞的募集并促进胆管结扎诱导的肝纤维化
DOI：
10.1038/s41419-020-03277-0
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发表时间：
2021-01-07
影响因子：
9
通讯作者：
Lv Z
中科院分区：
文献类型：
--
作者：
Mo C;Xie S;Liu B;Zhong W;Zeng T;Huang S;Lai Y;Deng G;Zhou C;Yan W;Chen Y;Huang S;Gao L;Lv Z
肝纤维化是一个慢性肝功能障碍的病程，可发展为肝硬变和肝细胞癌。致病因素引起的炎性损伤在肝纤维化的发病机制中起着重要作用。吲哚胺2，3-双加氧酶1(IDO1)可在多种疾病的病理过程中影响免疫细胞的渗透，但其在肝纤维化中的作用尚未完全阐明。在这里，肝脏中的IDO1蛋白显著升高，树突状细胞(DC)免疫表型在BDL攻击后发生了显著变化。肝脏CD11c+DC数量减少，呈不成熟免疫表型，共刺激分子(CD40、MHCII)表达水平降低。脾细胞CD11c+CD80+、CD11c+CD86+、CD11c+MHCII+、CD11c+CD40+细胞比例明显降低。值得注意的是，IDO1过表达抑制了肝、脾CD11c+DC的成熟，成熟DC介导的T细胞增殖，并加重了肝纤维化，而IDO1−/−小鼠的上述病理现象则相反。我们的数据表明，IDO1通过抑制DC的成熟和随后的T细胞增殖而影响免疫细胞的募集过程，从而促进肝纤维化。因此，靶向IDO1改善肝脾微环境的免疫反应可能是其治疗肝纤维化的关键。
Liver fibrosis is a course of chronic liver dysfunction, can develop into cirrhosis and hepatocellular carcinoma. Inflammatory insult owing to pathogenic factors plays a crucial role in the pathogenesis of liver fibrosis. Indoleamine 2,3-dioxygenase 1 (IDO1) can affect the infiltration of immune cells in many pathology processes of diseases, but its role in liver fibrosis has not been elucidated completely. Here, the markedly elevated protein IDO1 in livers was identified, and dendritic cells (DCs) immune-phenotypes were significantly altered after BDL challenge. A distinct hepatic population of CD11c+DCs was decreased and presented an immature immune-phenotype, reflected by lower expression levels of co-stimulatory molecules (CD40, MHCII). Frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+MHCII+, and CD11c+CD40+cells in splenic leukocytes were reduced significantly. Notably, IDO1 overexpression inhibited hepatic, splenic CD11c+DCs maturation, mature DCs-mediated T-cell proliferation and worsened liver fibrosis, whereas above pathological phenomena were reversed in IDO1−/−mice. Our data demonstrate that IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis. Thus, amelioration of immune responses in hepatic and splenic microenvironment by targeting IDO1 might be essential for the therapeutic effects on liver fibrosis.
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影响因子：
4.3
作者：
Guo, Gongliang;Sun, Liqun;Xu, Haiming
通讯作者：
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影响因子：
4.1
作者：
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Saad, Zienab Mostafa
DOI：
10.1111/j.1530-0277.2011.01472.x
发表时间：
2011-07-01
影响因子：
3.2
作者：
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影响因子：
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作者：
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影响因子：
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通讯作者：
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