Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model
Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model
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DOI：
10.1111/jgh.13183
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发表时间：
2016-03-01
影响因子：
4.1
通讯作者：
Liu, Yulan
中科院分区：
文献类型：
--
作者：
Hu, Ying;Zhang, Henghui;Liu, Yulan
背景与目的大多数研究集中在肠道衍生因子，如微生物区系及其产物，以及它们如何促进非酒精性脂肪性肝病(NAFLD)的进展。方法采用高脂饮食建立NAFLD小鼠模型，用1，1-二十八基-3，3，3，3，3-四甲基吲哚三碳菁碘和羧基荧光素琥珀酰亚胺酯标记淋巴细胞，静脉注射监测淋巴细胞迁移情况。NAFLD小鼠肝脏中枢记忆性CD4(+)T细胞和CD8(+)T细胞的频率显著增加，而活化的T细胞无明显变化。过继转移MLN细胞后，NAFLD受体小鼠肝脏中活化的CD4(+)T细胞和CD8(+)T细胞的频率增加。相比之下，中枢记忆和幼稚的CD4(+)T细胞和CD8(+)T细胞的频率下降。MLN细胞还诱导NAFLD受体小鼠的肝损伤，表现为血清丙氨酸转氨酶和谷草转氨酶升高。趋化实验表明CCL5介导了MLN细胞向肝脏的迁移。结论NAFLD小鼠GUT来源的淋巴细胞可迁移至肝脏，导致肝损伤及肝内CD4(+)T、CD8(+)T细胞活化。这种迁移与肝脏中CCL5的表达上调有关。
Background and AimMost studies focus on gut-derived factors like microbiota and its products and how they contribute to non-alcoholic fatty liver disease (NAFLD) progression. This study investigated whether the gut-derived lymphocytes could migrate to the liver and induce liver injury in NAFLD.MethodsA high-fat diet induced an NAFLD mouse model, and lymphocytes were labeled with 1,1-dioctadecyl-3,3,3,3 tetramethylindotricarbocyanine iodide and carboxy-fluorescein succinimidyl ester, respectively, and intravenously injected to mice to monitor lymphocyte migration.ResultsAdoptive transfer model results indicated that compared with lymphocytes from the spleen, bone marrow and thymus of NAFLD donor mice, mesenteric lymph nodes (MLN) cells from NAFLD donor mice predominately accumulated in the livers of NAFLD recipient mice. The frequencies of central memory CD4(+)T and CD8(+)T cells in livers of NAFLD mice were significantly increased; however, the activated T cells were not significantly altered. After adoptively transferred MLN cells, the frequencies of the activated CD4(+)T and CD8(+)T cells increased in livers of NAFLD recipient mice. By contrast, the frequencies of central memory and naive CD4(+)T and CD8(+)T cells decreased. MLN cells also induced liver injury in NAFLD recipient mice, as reflected by elevated serum alanine aminotransferase and glutamic oxaloacetic transaminase serums. Moreover, the chemotaxis assay showed that CCL5 mediated the MLN cell migration to the liver. Also, blocking the CCL5 inhibited MLN cell migration to the liver in vitro.ConclusionsGut-derived lymphocytes from NAFLD mice could migrate to the liver and induce liver injury and hepatic CD4(+)T and CD8(+)T cells activation. The migration was associated with the upregulation of CCL5 in the liver.