Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation.
Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation.
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DOI：
10.1002/hep4.1145
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发表时间：
2018-03
影响因子：
5.1
通讯作者：
Lafdil F
中科院分区：
文献类型：
--
作者：
Guillot A;Gasmi I;Brouillet A;Ait-Ahmed Y;Calderaro J;Ruiz I;Gao B;Lotersztajn S;Pawlotsky JM;Lafdil F
肝祖细胞（LPCs）/胆管反应（DRs）与炎症相关，并涉及慢性肝病的发病机制。然而，炎症如何调节LPCs/DRs在很大程度上仍然未知。确定涉及LPC激活和扩增的炎症过程是理解肝病发病机制的关键一步。在当前研究中，我们发现多种类型的慢性肝病与浸润的白细胞介素（IL）-17阳性（+）细胞和细胞角蛋白19（CK19）+ LPCs的增加有关，并且这两种细胞类型共定位，它们的数量彼此呈正相关。在喂食胆碱缺乏和补充乙硫氨酸（CDE）饮食的小鼠模型中研究了IL - 17在诱导LPCs中的作用。给野生型小鼠喂食CDE饮食显著增加了CK19 + Ki67 +增殖性LPCs和肝脏炎症。IL - 17基因或IL - 27受体α亚基（WSX - 1）基因的破坏消除了CDE饮食诱导的LPC扩增和炎症。IL - 17的体外处理促进了双潜能小鼠卵圆肝细胞（一种肝祖细胞系）的增殖，并显著上调了巨噬细胞中IL - 27的表达。IL - 27处理有利于双潜能小鼠卵圆肝细胞和新鲜分离的LPCs分化为肝细胞。结论：目前的数据为IL - 17和IL - 27分别在促进LPC扩增和分化方面的协同作用提供了证据，从而有助于肝脏再生。（《肝脏病学通讯》2018年；2：329 - 343）
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)‐17‐positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other. The role of IL‐17 in the induction of LPCs was examined in a mouse model fed a choline‐deficient and ethionine‐supplemented (CDE) diet. Feeding of wild‐type mice with the CDE diet markedly elevated CK19+Ki67+ proliferating LPCs and hepatic inflammation. Disruption of the IL‐17 gene or IL‐27 receptor, alpha subunit (WSX‐1) gene abolished CDE diet‐induced LPC expansion and inflammation. In vitro treatment with IL‐17 promoted proliferation of bipotential murine oval liver cells (a liver progenitor cell line) and markedly up‐regulated IL‐27 expression in macrophages. Treatment with IL‐27 favored the differentiation of bipotential murine oval liver cells and freshly isolated LPCs into hepatocytes. Conclusion: The current data provide evidence for a collaborative role between IL‐17 and IL‐27 in promoting LPC expansion and differentiation, respectively, thereby contributing to liver regeneration. (Hepatology Communications 2018;2:329‐343)
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影响因子：
13.5
作者：
Kong, Xiaoni;Feng, Dechun;Wang, Hua;Hong, Feng;Bertola, Adeline;Wang, Fu-Sheng;Gao, Bin
通讯作者：
Gao, Bin
影响因子：
6.7
作者：
Furusawa J;Mizoguchi I;Chiba Y;Hisada M;Kobayashi F;Yoshida H;Nakae S;Tsuchida A;Matsumoto T;Ema H;Mizuguchi J;Yoshimoto T
通讯作者：
Yoshimoto T
影响因子：
13.5
作者：
Clouston, AD;Powell, EE;Jonsson, JR
通讯作者：
Jonsson, JR
影响因子：
29.4
作者：
Meng F;Wang K;Aoyama T;Grivennikov SI;Paik Y;Scholten D;Cong M;Iwaisako K;Liu X;Zhang M;Österreicher CH;Stickel F;Ley K;Brenner DA;Kisseleva T
通讯作者：
Kisseleva T
影响因子：
13.5
作者：
Gadd, Victoria L.;Skoien, Richard;Clouston, Andrew D.
通讯作者：
Clouston, Andrew D.