The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42428-7 |
| _version_ | 1797558750170578944 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:35:56Z |
| format | Article |
| id | doaj.art-c7ad487a99994244b069b0dfc088305f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:35:56Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c7ad487a99994244b069b0dfc088305f2023-11-20T09:51:48ZengNature PortfolioNature Communications2041-17232023-10-0114112010.1038/s41467-023-42428-7The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cellsYan Wang0Quan Zhang1Tingting He2Yechen Wang3Tianqi Lu4Zengge Wang5Yiyi Wang6Shen Lin7Kang Yang8Xinming Wang9Jun Xie10Ying Zhou11Yazhen Hong12Wen-Hsien Liu13Kairui Mao14Shih-Chin Cheng15Xin Chen16Qiyuan Li17Nengming Xiao18State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityNational Institute for Data Science in Health and Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversitySchool of Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityNational Institute for Data Science in Health and Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityNational Institute for Data Science in Health and Medicine, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen UniversityAbstract 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.https://doi.org/10.1038/s41467-023-42428-7 |
| spellingShingle | 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 The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells Nature Communications |
| title | The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| title_full | The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| title_fullStr | The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| title_full_unstemmed | The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| title_short | The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| title_sort | transcription factor zeb1 controls homeostasis and function of type 1 conventional dendritic cells |
| url | https://doi.org/10.1038/s41467-023-42428-7 |
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