| Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. | |
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MedLine Citation:
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PMID: 22101768 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. |
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Authors:
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Natalia Shulzhenko; Andrey Morgun; William Hsiao; Michele Battle; Michael Yao; Oksana Gavrilova; Marlene Orandle; Lloyd Mayer; Andrew J Macpherson; Kathy D McCoy; Claire Fraser-Liggett; Polly Matzinger |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2011-11-20 |
Journal Detail:
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Title: Nature medicine Volume: 17 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-07 Completed Date: 2012-02-02 Revised Date: 2012-05-03 |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 1585-93 Citation Subset: IM |
Affiliation:
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'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, Maryland, USA. natalia.shulzhenko@oregonstate.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / immunology*, metabolism DNA, Bacterial / isolation & purification Epithelial Cells / immunology, microbiology GATA4 Transcription Factor / genetics, metabolism Gene Expression Profiling Gene Regulatory Networks Humans Immunoglobulin A / immunology Intestinal Mucosa / immunology*, metabolism, microbiology* Lipid Metabolism* Metagenome* Mice Mice, Inbred BALB C Mice, Knockout Microarray Analysis Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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P40RR018603/RR/NCRR NIH HHS; R01 DK087873/DK/NIDDK NIH HHS; U24 DK059630/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Bacterial; 0/GATA4 Transcription Factor; 0/Gata4 protein, mouse; 0/Immunoglobulin A |
| Comments/Corrections | |
Comment In:
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Nat Med. 2011 Dec;17(12):1549-50
[PMID:
22146454
]
Nat Rev Immunol. 2012 Jan;12(1):2 [PMID: 22193762 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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