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The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells.

Authors :
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
Source :
Nature Communications; 10/20/2023, Vol. 14 Issue 1, p1-20, 20p
Publication Year :
2023

Abstract

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<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
173149567
Full Text :
https://doi.org/10.1038/s41467-023-42428-7