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IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis : IL-33 regulates the IgA-microbiota axis to restrain IL-1 alpha-dependent colitis and tumorigenesis
DC Field | Value | Language |
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dc.contributor.author | Malik, Ankit | - |
dc.contributor.author | Sharma, Deepika | - |
dc.contributor.author | Zhu, Qifan | - |
dc.contributor.author | Karki, Rajendra | - |
dc.contributor.author | Guy, Clifford S. | - |
dc.contributor.author | Vogel, Peter | - |
dc.contributor.author | Kanneganti, Thirumala-Devi | - |
dc.date.accessioned | 2024-05-16T01:58:45Z | - |
dc.date.available | 2024-05-16T01:58:45Z | - |
dc.date.created | 2023-05-08 | - |
dc.date.created | 2023-05-08 | - |
dc.date.created | 2023-05-08 | - |
dc.date.issued | 2016-12 | - |
dc.identifier.citation | Journal of Clinical Investigation, Vol.126 No.12, pp.4469-4481 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://hdl.handle.net/10371/203045 | - |
dc.description.abstract | Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1 alpha, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1 alpha ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1 alpha-dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1 alpha, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC. | - |
dc.language | 영어 | - |
dc.publisher | American Society for Clinical Investigation | - |
dc.title | IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis | - |
dc.title.alternative | IL-33 regulates the IgA-microbiota axis to restrain IL-1 alpha-dependent colitis and tumorigenesis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1172/JCI88625 | - |
dc.citation.journaltitle | Journal of Clinical Investigation | - |
dc.identifier.wosid | 000390131900011 | - |
dc.identifier.scopusid | 2-s2.0-85002926045 | - |
dc.citation.endpage | 4481 | - |
dc.citation.number | 12 | - |
dc.citation.startpage | 4469 | - |
dc.citation.volume | 126 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Karki, Rajendra | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | AKKERMANSIA-MUCINIPHILA | - |
dc.subject.keywordPlus | INTESTINAL INFLAMMATION | - |
dc.subject.keywordPlus | ULCERATIVE-COLITIS | - |
dc.subject.keywordPlus | COLON INFLAMMATION | - |
dc.subject.keywordPlus | ADAPTIVE IMMUNITY | - |
dc.subject.keywordPlus | IMMUNOGLOBULIN-A | - |
dc.subject.keywordPlus | ENDOGENOUS IL-33 | - |
dc.subject.keywordPlus | CROHNS-DISEASE | - |
dc.subject.keywordPlus | OPEN-LABEL | - |
dc.subject.keywordPlus | RECEPTOR | - |
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