Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis

Abstract Inflammatory bowel disease (IBD) is a chronic, relapsing, and remitting disease characterized by chronic inflammation in the gastrointestinal tract. The exact etiology and pathogenesis of IBD remain elusive. Although ELF-1 has been known to be highly expressed in epithelial cells for past t...

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Main Authors: Gege He, Pingping Liu, Xiaoyan Xuan, Min Zhang, Hongxia Zhang, Ka Yang, Yusheng Luan, Qian Yang, Jingyuan Yang, Qianru Li, Huaixin Zheng, Peng Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07742-4
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author Gege He
Pingping Liu
Xiaoyan Xuan
Min Zhang
Hongxia Zhang
Ka Yang
Yusheng Luan
Qian Yang
Jingyuan Yang
Qianru Li
Huaixin Zheng
Peng Wang
author_facet Gege He
Pingping Liu
Xiaoyan Xuan
Min Zhang
Hongxia Zhang
Ka Yang
Yusheng Luan
Qian Yang
Jingyuan Yang
Qianru Li
Huaixin Zheng
Peng Wang
author_sort Gege He
collection DOAJ
description Abstract Inflammatory bowel disease (IBD) is a chronic, relapsing, and remitting disease characterized by chronic inflammation in the gastrointestinal tract. The exact etiology and pathogenesis of IBD remain elusive. Although ELF-1 has been known to be highly expressed in epithelial cells for past twenty years, little is known about its function in epithelial cells and epithelial-related IBD. Here, we demonstrated that ELF-1 deficiency in mouse lead to exacerbated DSS-induced colitis, marked by inflammation dominated by neutrophil infiltration and activation of IL-17 signaling pathways in various immune cells, including Th17, ILC3, γδT and NKT cells. Bone marrow transfer experiments confirmed ELF-1 deficiency in non-hematopoietic cells intrinsically worsened DSS-induced colitis. On one hand, ELF-1 deficiency enhanced the production of pro-inflammatory chemokines in colonic epithelial cells, leading to extensive infiltration of neutrophils and other immune cells into the colonic mucosal tissue. On the other hand, ELF-1 directly regulated the expression of the Rack1 gene in colonic epithelial tissue, which has been proved to play critical roles in maintaining intestinal homeostasis. Altogether, ELF-1 plays a protective role in colitis by maintaining intestinal epithelium homeostasis.
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spelling doaj-art-90649d52bd7141b7b74606d8b63f45f72025-08-20T02:59:57ZengNature PortfolioCommunications Biology2399-36422025-03-018111210.1038/s42003-025-07742-4Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasisGege He0Pingping Liu1Xiaoyan Xuan2Min Zhang3Hongxia Zhang4Ka Yang5Yusheng Luan6Qian Yang7Jingyuan Yang8Qianru Li9Huaixin Zheng10Peng Wang11Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou UniversityAbstract Inflammatory bowel disease (IBD) is a chronic, relapsing, and remitting disease characterized by chronic inflammation in the gastrointestinal tract. The exact etiology and pathogenesis of IBD remain elusive. Although ELF-1 has been known to be highly expressed in epithelial cells for past twenty years, little is known about its function in epithelial cells and epithelial-related IBD. Here, we demonstrated that ELF-1 deficiency in mouse lead to exacerbated DSS-induced colitis, marked by inflammation dominated by neutrophil infiltration and activation of IL-17 signaling pathways in various immune cells, including Th17, ILC3, γδT and NKT cells. Bone marrow transfer experiments confirmed ELF-1 deficiency in non-hematopoietic cells intrinsically worsened DSS-induced colitis. On one hand, ELF-1 deficiency enhanced the production of pro-inflammatory chemokines in colonic epithelial cells, leading to extensive infiltration of neutrophils and other immune cells into the colonic mucosal tissue. On the other hand, ELF-1 directly regulated the expression of the Rack1 gene in colonic epithelial tissue, which has been proved to play critical roles in maintaining intestinal homeostasis. Altogether, ELF-1 plays a protective role in colitis by maintaining intestinal epithelium homeostasis.https://doi.org/10.1038/s42003-025-07742-4
spellingShingle Gege He
Pingping Liu
Xiaoyan Xuan
Min Zhang
Hongxia Zhang
Ka Yang
Yusheng Luan
Qian Yang
Jingyuan Yang
Qianru Li
Huaixin Zheng
Peng Wang
Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
Communications Biology
title Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
title_full Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
title_fullStr Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
title_full_unstemmed Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
title_short Transcription factor ELF-1 protects against colitis by maintaining intestinal epithelium homeostasis
title_sort transcription factor elf 1 protects against colitis by maintaining intestinal epithelium homeostasis
url https://doi.org/10.1038/s42003-025-07742-4
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