The Transcription Factor Zeb1 Controls Homeostasis and Function of Type 1 Conventional Dendritic Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Oct 20

PMID 37863917

Authors

Yan Wang

Quan Zhang

Tingting He

Yechen Wang

Tianqi Lu

Zengge Wang

Yiyi Wang

Shen Lin

Kang Yang

Xinming Wang

Jun Xie

Ying Zhou

Yazhen Hong

Wen-Hsien Liu

Kairui Mao

Shih-Chin Cheng

Xin Chen

Qiyuan Li

Nengming Xiao

Affiliations

Soon will be listed here.

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 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.

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