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PMID: 22101768 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut.

Nature medicine ·Vol. 17 ·No. 12 ·2011-11-20 ·Pages 1585-93

Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O, Orandle M, Mayer L, Macpherson AJ, McCoy KD, Fraser-Liggett C, Matzinger P

Abstract

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.

MeSH Terms
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
Chemicals
DNA, Bacterial GATA4 Transcription Factor Gata4 protein, mouse Immunoglobulin A
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Shulzhenko Natalia
'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. [email protected]
Morgun Andrey
Hsiao William
Battle Michele
Yao Michael
Gavrilova Oksana
Orandle Marlene
Mayer Lloyd
Macpherson Andrew J
McCoy Kathy D
Fraser-Liggett Claire
Matzinger Polly
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.2505
Email
[email protected]
Published
2011-11-20
Epub
2011-00-20
Pages
1585-93
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC3902046
Subset
IM
Grants
NIDDK NIH HHS · U24 DK059630 · United States
Intramural NIH HHS · Z01 AI000581-20 · United States
NCRR NIH HHS · P40 RR018603 · United States
NIDDK NIH HHS · R01 DK087873 · United States
NCRR NIH HHS · P40RR018603 · United States
Corrections
CommentIn
PMID: 22146454
CommentIn
PMID: 22193762
External Links
PubMed source DOI: 10.1038/nm.2505 PMC Full Text View journal details
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