Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells
Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells
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肝脏驻留 NK 细胞抑制自身免疫性胆管炎并限制 CD4 T 细胞的增殖
DOI：
10.1038/s41423-019-0199-z
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发表时间：
2019-03
影响因子：
24.1
通讯作者：
Lian Zhe-Xiong
中科院分区：
文献类型：
--
作者：
Zhao Zhi-Bin;Lu Fang-Ting;Ma Hong-Di;Wang Yin-Hu;Yang Wei;Long Jie;Miao Qi;Zhang Wei-Ci;Tian Zhi-Gang;Ridgway William M;Cao Jie;Gershwin M. Eric;Lian Zhe-Xiong
肝驻留NK细胞不同于传统NK细胞，在维持肝脏稳态中发挥重要作用。肝脏NK细胞如何参与自身免疫性胆管炎尚不清楚。在这里，我们利用完善的dnTGFβRII胆管炎模型、NK细胞缺陷（Nfil3-/-）小鼠、过继性转移和体内抗体介导的NK细胞耗损，广泛研究了NK细胞在自身免疫性胆管炎发病机制中的影响。我们的数据表明，疾病进展与肝NK细胞频率显著降低有关。NK细胞耗竭导致dnTGFβRII小鼠自身免疫性胆管炎加重。我们进一步证实了dx5 - cd11chiliaver驻留NK细胞亚群与CD4+T细胞共定位并抑制CD4+T细胞增殖。基因表达微阵列分析表明，肝脏NK细胞具有独特的基因表达模式，包括炎症微环境下参与负调控功能的基因表达增加。
Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver homeostasis. How liver-resident NK cells participate in autoimmune cholangitis remains unclear. Here, we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model, NK cell-deficient (Nfil3-/-) mice, adoptive transfer and in vivo antibody-mediated NK cell depletion. Our data demonstrated that disease progression was associated with a significantly reduced frequency of hepatic NK cells. Depletion of NK cells resulted in exacerbated autoimmune cholangitis in dnTGFβRII mice. We further confirmed that the DX5-CD11chiliver-resident NK cell subset colocalized with CD4+T cells and inhibited CD4+T cell proliferation. Gene expression microarray analysis demonstrated that liver-resident NK cells had a distinct gene expression pattern consisting of the increased expression of genes involved in negative regulatory functions in the context of the inflammatory microenvironment.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
13.5
作者：
Shimoda, Shinji;Harada, Kenichi;Niiro, Hiroaki;Shirabe, Ken;Taketomi, Akinobu;Maehara, Yoshihiko;Tsuneyama, Koichi;Nakanuma, Yasuni;Leung, Patrick;Ansari, Aftab A.;Gershwin, M. Eric;Akashi, Koichi
通讯作者：
Akashi, Koichi
NFIL3/E4BP4是在体内开发和成熟所必需的。
DOI：
10.1084/jem.20092176
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kamizono S;Duncan GS;Seidel MG;Morimoto A;Hamada K;Grosveld G;Akashi K;Lind EF;Haight JP;Ohashi PS;Look AT;Mak TW
通讯作者：
Mak TW
影响因子：
13.5
作者：
Kawata, Kazuhito;Yang, Guo-Xiang;Ando, Yugo;Tanaka, Hajime;Zhang, Weici;Kobayashi, Yoshimasa;Tsuneyama, Koichi;Leung, Patrick S. C.;Lian, Zhe-Xiong;Ridgway, William M.;Ansari, Aftab A.;He, Xiao-Song;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
13.5
作者：
Y. Chuang;Zhe‐Xiong Lian;Guo‐Xiang-X. Yang;S. Shu;Y. Moritoki;W. Ridgway;A. Ansari;M. Kronenberg;R. Flavell;B. Gao;M. Gershwin
通讯作者：
Y. Chuang;Zhe‐Xiong Lian;Guo‐Xiang-X. Yang;S. Shu;Y. Moritoki;W. Ridgway;A. Ansari;M. Kronenberg;R. Flavell;B. Gao;M. Gershwin