The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells.
The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells.
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DOI：
10.1038/s41467-023-42428-7
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发表时间：
2023-10-20
影响因子：
16.6
通讯作者：
Xiao, Nengming
中科院分区：
文献类型：
--
作者：
Wang, Yan;Zhang, Quan;He, Tingting;Wang, Yechen;Lu, Tianqi;Wang, Zengge;Wang, Yiyi;Lin, Shen;Yang, Kang;Wang, Xinming;Xie, Jun;Zhou, Ying;Hong, Yazhen;Liu, Wen-Hsien;Mao, Kairui;Cheng, Shih-Chin;Chen, Xin;Li, Qiyuan;Xiao, Nengming
1型常规树突状细胞（cDC 1）是诱导保护性细胞毒性T细胞应答的最有效的交叉呈递细胞。然而，它们的稳态和功能的调节并不完全清楚。在这里，我们观察到选择性减少脾脏cDC 1伴随着过度的细胞死亡，在树突状细胞Zeb 1缺陷的小鼠，使小鼠更耐李斯特菌感染。此外，来自Zeb 1缺陷小鼠的其他来源的cDC 1显示外源性抗原的交叉呈递受损，损害抗肿瘤CD 8 + T细胞应答。从机制上讲，Zeb 1抑制靶向NADPH氧化酶Nox 2的Cybb mRNA的microRNA-96/182的表达，从而促进吞噬体膜的活性氧依赖性破裂，以允许抗原输出到胞质溶胶。Cybb在Zeb 1缺陷型cDC 1中的再表达完全恢复了缺陷型交叉呈递，而microRNA-96/182在Zeb 1充足型cDC 1中的过表达抑制了交叉呈递。因此，我们的研究结果确定了一个Zeb 1-microRNA-96/182-Cybb通路，控制cDC 1中的交叉呈递，并揭示了Zeb 1在cDC 1稳态中的重要作用。1型常规树突状细胞（cDC 1）在抗原的交叉呈递中发挥关键作用，使有效的CD 8 + T细胞应答成为可能。在这里，作者表明，转录因子Zeb 1基本上通过促进吞噬体膜的活性氧依赖性破裂来调节这一过程，以允许抗原输出到细胞质。
Type 1 conventional dendritic cells (cDC1) are the most efficient cross-presenting cells that induce protective cytotoxic T cell response. However, the regulation of their homeostasis and function is incompletely understood. Here we observe a selective reduction of splenic cDC1 accompanied by excessive cell death in mice with Zeb1 deficiency in dendritic cells, rendering the mice more resistant to Listeria infection. Additionally, cDC1 from other sources of Zeb1-deficient mice display impaired cross-presentation of exogenous antigens, compromising antitumor CD8+ T cell responses. Mechanistically, Zeb1 represses the expression of microRNA-96/182 that target Cybb mRNA of NADPH oxidase Nox2, and consequently facilitates reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytosol. Cybb re-expression in Zeb1-deficient cDC1 fully restores the defective cross-presentation while microRNA-96/182 overexpression in Zeb1-sufficient cDC1 inhibits cross-presentation. Therefore, our results identify a Zeb1-microRNA-96/182-Cybb pathway that controls cross-presentation in cDC1 and uncover an essential role of Zeb1 in cDC1 homeostasis. Type 1 conventional dendritic cells (cDC1) play a pivotal role in the cross-presentation of antigens, enabling efficient CD8 + T cell response. Here authors show that the transcription factor Zeb1 essentially regulates this process via facilitating the reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytoplasm.
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DOI：
10.1073/pnas.1619863114
发表时间：
2017-04-11
影响因子：
11.1
作者：
Briseno, Carlos G.;Gargaro, Marco;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.
影响因子：
30.5
作者：
Grajales-Reyes GE;Iwata A;Albring J;Wu X;Tussiwand R;Kc W;Kretzer NM;Briseño CG;Durai V;Bagadia P;Haldar M;Schönheit J;Rosenbauer F;Murphy TL;Murphy KM
通讯作者：
Murphy KM
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
18.4
作者：
Böttcher JP;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
4.6
作者：
Dingjan I;Verboogen DR;Paardekooper LM;Revelo NH;Sittig SP;Visser LJ;Mollard GF;Henriet SS;Figdor CG;Ter Beest M;van den Bogaart G
通讯作者：
van den Bogaart G