Immune Regulation of Intrahepatic Regulatory T Cells in Fibrotic Livers of Mice.
Immune Regulation of Intrahepatic Regulatory T Cells in Fibrotic Livers of Mice.
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小鼠纤维化肝脏中肝内调节性 T 细胞的免疫调节
DOI：
10.12659/msm.899725
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发表时间：
2017-02-25
期刊：
影响因子：
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通讯作者：
Duan Z
中科院分区：
文献类型：
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作者：
Zhang X;Lou J;Bai L;Chen Y;Zheng S;Duan Z
肝纤维化是慢性炎症和修复的结果，许多免疫细胞参与了这一过程。调节性T细胞（Tcells）介导免疫耐受，并在肝纤维化中高度表达。然而，很少有报道研究THBE在肝纤维化中调节免疫细胞的特异性作用。本研究旨在通过清除Tcl 3，探讨Tcl 3对肝纤维化小鼠肝内免疫细胞的调节作用。用四氯化碳诱导肝纤维化，并使用抗CD 25 mAb（PC 61）来消耗THP。免疫荧光染色和丙氨酸氨基转移酶水平反映肝纤维化和肝损伤。采用流式细胞术和/或实时荧光定量PCR检测免疫细胞TGFAP和细胞因子的表达。用ELISA法测定干扰素-γ（IFN-γ）浓度。肝纤维化肝脏中富含Tcl 3; Tcl 3耗竭后，肝内CD 4 + T细胞和Kupffer细胞（KC）数量与肝纤维化相比没有变化，但CD 8 + T细胞略有升高。然而，自然杀伤（NK）细胞和IFN-γ水平在纤维化中显著降低，并且在Tcl 3耗竭后增加。有趣的是，我们发现TdR促进KC M1/M2平衡到M2，因为在耗尽TdR后诱导型一氧化氮合酶（M1）增加，而一氧化氮酶-1（M2）减少。此外，与纤维化肝脏相比，在从肝脏分离的KCs中，在耗尽TlR后，IL-12（M1）增加，但TGF-β（M2）减少。T细胞参与肝纤维化的免疫调节，主要通过抑制NK细胞和M1 KCs，并轻度抑制CD 8 + T细胞。
Liver fibrosis is the result of chronic inflammation and repair, and many immune cells contribute to the process. Regulatory T cells (Tregs) mediate immune tolerance and are highly expressed in liver fibrosis. However, few reports have studied the specific effects of Tregs on regulating immune cells in liver fibrosis. The present study aimed to investigate the regulation of Tregs on intrahepatic immune cells in liver fibrosis by depleting Tregs in mice. Liver fibrosis was induced by carbon tetrachloride, and an anti-CD25 mAb (PC61) was used to deplete Tregs. Liver fibrosis and injury were reflected by immunofluorescence staining and alanine aminotransferase level. The expressions of immune cell Tregs and cytokines were detected by flow cytometry and/or real-time PCR. Interferon-γ (IFN-γ) concentration was measured by ELISA. Tregs were rich in fibrotic livers; after Tregs depletion, the intrahepatic CD4+ T cell and Kupffer cells (KC) populations did not change compared with liver fibrosis, but CD8+ T cells were slightly elevated. However, natural killer (NK) cells and IFN-γ levels were significantly decreased in fibrosis and increased after Tregs depletion. Interesting, we found Tregs promoted KC M1/M2 balance to M2, because inducible nitric oxide synthase (M1) was increased but arginase-1 (M2) was reduced after depleting Tregs. Furthermore, in isolated KCs from livers, IL-12 (M1) was increased, but TGF-β (M2) was reduced after depleting Tregs, compared with fibrotic livers. Tregs are involved in the immune regulation of liver fibrosis, primarily by suppressing NK cells and M1 KCs, and mildly suppressing CD8+ T cells.
HBV和HCV感染引起的肝炎后肝硬化的免疫学特征
影响因子：
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作者：
Li WY;Jiang YF;Jin QL;Zhang H;Feng XW;Niu JQ
通讯作者：
Niu JQ