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

Shulzhenko, Natalia; 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 (2011). Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nature medicine, 17(12), pp. 1585-93. New York, N.Y.: Nature Publishing Group 10.1038/nm.2505

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Macpherson, Andrew

ISSN:

1078-8956

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

17 Mar 2015 21:01

Publisher DOI:

10.1038/nm.2505

PubMed ID:

22101768

Web of Science ID:

000297978000029

URI:

https://boris.unibe.ch/id/eprint/7751 (FactScience: 213077)

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