Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides
Abstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40565-7 |
| _version_ | 1827710149897224192 |
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| author | Yue Wang Yanbo Yu Lixiang Li Mengqi Zheng Jiawei Zhou Haifan Gong Bingcheng Feng Xiao Wang Xuanlin Meng Yanyan Cui Yanan Xia Shuzheng Chu Lin Lin Huijun Chang Ruchen Zhou Mingjun Ma Zhen Li Rui Ji Ming Lu Xiaoyun Yang Xiuli Zuo Shiyang Li Yanqing Li |
| author_facet | Yue Wang Yanbo Yu Lixiang Li Mengqi Zheng Jiawei Zhou Haifan Gong Bingcheng Feng Xiao Wang Xuanlin Meng Yanyan Cui Yanan Xia Shuzheng Chu Lin Lin Huijun Chang Ruchen Zhou Mingjun Ma Zhen Li Rui Ji Ming Lu Xiaoyun Yang Xiuli Zuo Shiyang Li Yanqing Li |
| author_sort | Yue Wang |
| collection | DOAJ |
| description | Abstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease. |
| first_indexed | 2024-03-10T17:33:07Z |
| format | Article |
| id | doaj.art-f3d20c2f1ec949bf996021992802ed53 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:33:07Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f3d20c2f1ec949bf996021992802ed532023-11-20T09:57:34ZengNature PortfolioNature Communications2041-17232023-08-0114111610.1038/s41467-023-40565-7Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptidesYue Wang0Yanbo Yu1Lixiang Li2Mengqi Zheng3Jiawei Zhou4Haifan Gong5Bingcheng Feng6Xiao Wang7Xuanlin Meng8Yanyan Cui9Yanan Xia10Shuzheng Chu11Lin Lin12Huijun Chang13Ruchen Zhou14Mingjun Ma15Zhen Li16Rui Ji17Ming Lu18Xiaoyun Yang19Xiuli Zuo20Shiyang Li21Yanqing Li22Department of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversitySchool of Computer Science and Engineering, Sun Yat-sen UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Pathology, Qilu Hospital of Shandong UniversityState Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityAdvanced Medical Research Institute, Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityAdvanced Medical Research Institute, Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityDepartment of Gastroenterology, Qilu Hospital of Shandong UniversityAbstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.https://doi.org/10.1038/s41467-023-40565-7 |
| spellingShingle | Yue Wang Yanbo Yu Lixiang Li Mengqi Zheng Jiawei Zhou Haifan Gong Bingcheng Feng Xiao Wang Xuanlin Meng Yanyan Cui Yanan Xia Shuzheng Chu Lin Lin Huijun Chang Ruchen Zhou Mingjun Ma Zhen Li Rui Ji Ming Lu Xiaoyun Yang Xiuli Zuo Shiyang Li Yanqing Li Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides Nature Communications |
| title | Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| title_full | Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| title_fullStr | Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| title_full_unstemmed | Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| title_short | Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| title_sort | bile acid dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides |
| url | https://doi.org/10.1038/s41467-023-40565-7 |
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