Interleukin 17-producing γδT cells promote hepatic regeneration in mice.
Interleukin 17-producing γδT cells promote hepatic regeneration in mice.
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产生白细胞介素 17 的 γδT 细胞促进小鼠肝脏再生。
DOI：
10.1053/j.gastro.2014.04.042
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发表时间：
2014-08
期刊：
影响因子：
29.4
通讯作者：
Miller G
中科院分区：
文献类型：
--
作者：
Rao R;Graffeo CS;Gulati R;Jamal M;Narayan S;Zambirinis CP;Barilla R;Deutsch M;Greco SH;Ochi A;Tomkötter L;Blobstein R;Avanzi A;Tippens DM;Gelbstein Y;Van Heerden E;Miller G
白细胞亚群与再生生长因子协同促进肝再生。在许多情况下，γδT细胞是炎症诱导的损伤的早期应答者。我们使用Tcrd（编码T细胞受体δ链）和Clec 7a（编码C型凝集素结构域家族7成员a，也称为DECTIN 1）中断的小鼠研究了γδT细胞在肝再生中的作用。我们对野生型C57 BL/6、CD45.1、Tcrd−/−或Clec 7a −/−小鼠进行了部分肝切除术。通过机械和酶消化从患者和小鼠的肝脏分离细胞。通过荧光激活细胞分选纯化γδT细胞。在小鼠中，部分肝切除上调CCL 20和Dectin-1配体的表达，与γδT细胞的募集和活化及其白细胞介素（IL）17家族细胞因子的产生增加相关。募集的γδT细胞诱导抗原呈递细胞产生IL 6，并抑制自然杀伤T细胞表达干扰素γ，促进肝细胞增殖。产生IL 17的γδT细胞的缺失或Dectin-1的缺失阻止了先天免疫细胞亚群中再生表型的发展。这减缓了肝再生，并与再生生长因子和细胞周期调节因子的表达减少有关。相反，外源性施用IL 17家族细胞因子或Dectin-1配体促进再生。更广泛地说，我们发现γδT细胞是IL 17和Dectin-1介导的炎症反应所必需的。γδT细胞通过产生IL 22和IL 17调节肝再生，IL 22和IL 17分别对肝细胞具有直接的促有丝分裂作用并促进肝白细胞的再生表型。Dectin-1连接是γδT细胞促进肝再生所必需的。
Subsets of leukocytes synergize with regenerative growth factors to promote hepatic regeneration. γδT cells are early responders to inflammation-induced injury in a number of contexts. We investigated the role of γδT cells in hepatic regeneration using mice with disruptions in Tcrd (encodes the T cell receptor δ chain) and Clec7a (encodes C-type lectin domain family 7 member a, also known as DECTIN1). We performed partial hepatectomies on wild-type C57BL/6, CD45.1, Tcrd−/−, or Clec7a−/− mice. Cells were isolated from livers of patients and mice via mechanical and enzymatic digestion. γδT cells were purified by fluorescence-activated cell sorting. In mice, partial hepatectomy upregulated expression of CCL20 and ligands of Dectin-1, associated with recruitment and activation of γδT cells and their increased production of interleukin (IL)17 family cytokines. Recruited γδT cells induced production of IL6 by antigen-presenting cells and suppressed expression of interferon γ by natural killer T cells, promoting hepatocyte proliferation. Absence of IL17-producing γδT cells or deletion of Dectin-1 prevented development of regenerative phenotypes in subsets of innate immune cells. This slowed liver regeneration and was associated with reduced expression of regenerative growth factors and cell cycle regulators. Conversely, exogenous administration of IL17 family cytokines or Dectin-1 ligands promoted regeneration. More broadly, we found that γδT cells are required for inflammatory responses mediated by IL17 and Dectin-1. γδT cells regulate hepatic regeneration by producing IL22 and IL17, which have direct mitogenic effects on hepatocytes and promote a regenerative phenotype in hepatic leukocytes, respectively. Dectin-1 ligation is required for γδT cells to promote hepatic regeneration.
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DOI：
10.1002/lt.23813
发表时间：
2014-03
期刊：
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
影响因子：
--
作者：
Wolf JH;Bhatti TR;Fouraschen S;Chakravorty S;Wang L;Kurian S;Salomon D;Olthoff KM;Hancock WW;Levine MH
通讯作者：
Levine MH
影响因子：
3.1
作者：
Gessner, Melissa A.;Werner, Jessica L.;Steele, Chad
通讯作者：
Steele, Chad
HBV 转基因小鼠肝脏再生受损与激活的肝脏 NKT 细胞相关
影响因子：
13.5
作者：
Dong, Zhongjun;Zhang, Jianhong;Tian, Zhigang
通讯作者：
Tian, Zhigang
影响因子：
5.4
作者：
Koenecke, Christian;Chennupati, Vijaykumar;Prinz, Immo
通讯作者：
Prinz, Immo
影响因子：
10.8
作者：
Thiagarajan, Praveena S.;Yakubenko, Valentin P.;Cathcart, Martha K.
通讯作者：
Cathcart, Martha K.