Combinatorial effects of interleukin 10 and interleukin 4 determine the progression of hepatic inflammation following murine enteric parasitic infection.
Combinatorial effects of interleukin 10 and interleukin 4 determine the progression of hepatic inflammation following murine enteric parasitic infection.
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DOI：
10.1002/hep.23576
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发表时间：
2010-06
期刊：
影响因子：
13.5
通讯作者：
Bliss, Susan K.
中科院分区：
文献类型：
--
作者：
Douglas, Diana B.;Beiting, Daniel P.;Loftus, John P.;Appleton, Judith A.;Bliss, Susan K.
缺乏免疫调节细胞因子IL-10的小鼠在感染旋毛虫后发生坏死性肝炎，并且炎症依赖于经阴道活化的CD 4 + T细胞迁移到肝脏中。在这些小鼠中，肝脏产生的IL-4升高，我们假设它在肝脏病理学的发展中起作用。口服感染野生型（WT）、IL-10敲除（KO）、IL-4 KO和IL-10/IL-4 KO小鼠，并通过组织学、丙氨酸氨基转移酶（ALT）测定和肝细胞内容物的流式细胞术分析跟踪疾病进展。IL-10 KO和IL-10/IL-4 KO小鼠均经历肝细胞损伤，但仅IL-10 KO小鼠进展至坏死期。肝脏CD 4 + T细胞是IL-4的主要来源，IL-10调节肝脏来源的CD 4 +IL-4+细胞的数量。激活的中性粒细胞在肝脏中的隔离需要IL-4，中性粒细胞耗竭防止进展到明显的坏死。肠道WT CD 4 + T细胞的连续转移抑制中性粒细胞积聚和炎症，但它们的调节作用不需要IL-10信号传导。IL-10的缺乏导致肝细胞在感染过程中的损伤，但IL-4是必要的嗜中性粒细胞依赖性坏死的发展。这些研究为这些细胞因子及其靶标在肝脏炎症的产生和进展中的组合作用提供了新的见解。
Mice lacking the immunoregulatory cytokine, IL-10, develop necrotizing hepatitis following infection with Trichinella spiralis, and inflammation is dependent on migration of intestinally activated CD4+ T cells into the liver. Hepatic production of IL-4 is elevated in these mice, and we hypothesized that it plays a role in the development of hepatic pathology. Wildtype (WT), IL-10 knockout (KO), IL-4 KO, and IL-10/IL-4 KO mice were orally infected, and disease progression was followed by histology, alanine aminotransferase (ALT) assays, and flow cytometric analysis of hepatocellular content. Both IL-10 KO and IL-10/IL-4 KO mice experienced hepatocellular injury, but only IL-10 KO mice advanced to a necrotic phase. Hepatic CD4+ T cells were the major source of IL-4, and IL-10 regulated the number of intestinally-derived CD4+IL-4+ cells. Sequestration of activated neutrophils in the liver required IL-4, and neutrophil depletion prevented progression to overt necrosis. Adoptive transfer of intestinal WT CD4+ T cells inhibited neutrophil accumulation and inflammation, but their regulatory effects did not require IL-10 signaling. The absence of IL-10 led to hepatocyte injury during infection, but IL-4 was necessary for the development of neutrophil-dependent necrosis. These studies provide new insight into the combinatorial role of these cytokines and their targets in the generation and progression of hepatic inflammation.
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肠道相关淋巴组织（GALT）中的肠道热带T细胞的选择性生成：对Galt树突状细胞和辅助的需求。
影响因子：
15.3
作者：
Johansson-Lindbom, B;Svensson, M;Wurbel, MA;Malissen, B;Márquez, G;Agace, W
通讯作者：
Agace, W
影响因子：
5
作者：
Chakravarti, Arpita;Rusu, Daniel;Poubelle, Patrice E.
通讯作者：
Poubelle, Patrice E.
影响因子：
4.4
作者：
Jaruga, B;Hong, F;Gao, B
通讯作者：
Gao, B
影响因子：
4.4
作者：
Zhai, Yuan;Shen, Xiu-da;Kupiec-Weglinski, Jerzy W.
通讯作者：
Kupiec-Weglinski, Jerzy W.
影响因子：
3.1
作者：
McFarlane, Emma;Perez, Cynthia;Tacchini-Cottier, Fabienne
通讯作者：
Tacchini-Cottier, Fabienne