AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis
Alpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut....
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2460538 |
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| author | Manikandan Palrasu Khadija Kakar Amarnath Marudamuthu Hamida Hamida Shruthi Thada Yin Zhong Shanieka Staley Philip Brandon Busbee Jie Li Monica Garcia-Buitrago Mitzi Nagarkatti Prakash Nagarkatti |
| author_facet | Manikandan Palrasu Khadija Kakar Amarnath Marudamuthu Hamida Hamida Shruthi Thada Yin Zhong Shanieka Staley Philip Brandon Busbee Jie Li Monica Garcia-Buitrago Mitzi Nagarkatti Prakash Nagarkatti |
| author_sort | Manikandan Palrasu |
| collection | DOAJ |
| description | Alpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut. The gut microbial products also serve as ligands for the aryl hydrocarbon receptor (AhR), an environmental sensor. In the current study, we investigated if there is any crosstalk between AhR and alpha-defensin 1. Interestingly, we found a positive correlation between AhR and alpha-defensin 1 protein levels in ileal tissues from active Crohn’s’ (CD) patients and epithelial cells (IECs) from multiple models of murine colitis. In vitro downregulation of AhR led to inhibition of α-defensin 1, while activation of AhR induced α-defensin 1 in IECs. AhR directly targeted the dioxin response element 3 (DRE3) region on the α-defensin 1 promoter in IECs. AhR-mediated induction of α-defensin 1 in colitis mice reversed the gut microbial dysbiosis and alleviated colitis. Our data identify a novel signaling pathway in which AhR acts as a transcription factor for α-defensin 1, leading to regulation of homeostasis between gut microbiota, intestinal mucosa, and mucosal immunity. |
| format | Article |
| id | doaj-art-2d6ee0fdadd640e19805f16c4fb35399 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-2d6ee0fdadd640e19805f16c4fb353992025-02-03T04:02:38ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2460538AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and ColitisManikandan Palrasu0Khadija Kakar1Amarnath Marudamuthu2Hamida Hamida3Shruthi Thada4Yin Zhong5Shanieka Staley6Philip Brandon Busbee7Jie Li8Monica Garcia-Buitrago9Mitzi Nagarkatti10Prakash Nagarkatti11Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USADepartment of Pathology, University of Miami Miller School of Medicine, Miami, Florida, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USADepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, USAAlpha-defensin 1 is a small antimicrobial peptide that acts as the first line of defense against pathogens. It is induced following microbial cues and inflammatory signals in neutrophils and Paneth cells in the small intestine, which suggests that it plays a role in microbial homeostasis in the gut. The gut microbial products also serve as ligands for the aryl hydrocarbon receptor (AhR), an environmental sensor. In the current study, we investigated if there is any crosstalk between AhR and alpha-defensin 1. Interestingly, we found a positive correlation between AhR and alpha-defensin 1 protein levels in ileal tissues from active Crohn’s’ (CD) patients and epithelial cells (IECs) from multiple models of murine colitis. In vitro downregulation of AhR led to inhibition of α-defensin 1, while activation of AhR induced α-defensin 1 in IECs. AhR directly targeted the dioxin response element 3 (DRE3) region on the α-defensin 1 promoter in IECs. AhR-mediated induction of α-defensin 1 in colitis mice reversed the gut microbial dysbiosis and alleviated colitis. Our data identify a novel signaling pathway in which AhR acts as a transcription factor for α-defensin 1, leading to regulation of homeostasis between gut microbiota, intestinal mucosa, and mucosal immunity.https://www.tandfonline.com/doi/10.1080/19490976.2025.2460538The aryl hydrocarbon receptorinflammatory bowel diseaseα-defensin 1colitiscrohn’s diseasemicrobiome |
| spellingShingle | Manikandan Palrasu Khadija Kakar Amarnath Marudamuthu Hamida Hamida Shruthi Thada Yin Zhong Shanieka Staley Philip Brandon Busbee Jie Li Monica Garcia-Buitrago Mitzi Nagarkatti Prakash Nagarkatti AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis Gut Microbes The aryl hydrocarbon receptor inflammatory bowel disease α-defensin 1 colitis crohn’s disease microbiome |
| title | AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis |
| title_full | AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis |
| title_fullStr | AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis |
| title_full_unstemmed | AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis |
| title_short | AhR Activation Transcriptionally Induces Anti-Microbial Peptide Alpha-Defensin 1 Leading to Reversal of Gut Microbiota Dysbiosis and Colitis |
| title_sort | ahr activation transcriptionally induces anti microbial peptide alpha defensin 1 leading to reversal of gut microbiota dysbiosis and colitis |
| topic | The aryl hydrocarbon receptor inflammatory bowel disease α-defensin 1 colitis crohn’s disease microbiome |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2460538 |
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