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Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med 2011 Nov 20;17(12):1585-93

Date

11/22/2011

Pubmed ID

22101768

Pubmed Central ID

PMC3902046

DOI

10.1038/nm.2505

Scopus ID

2-s2.0-84856083002   254 Citations

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.

Author List

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

Author

Michele A. Battle PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
B-Lymphocytes
DNA, Bacterial
Epithelial Cells
GATA4 Transcription Factor
Gene Expression Profiling
Gene Regulatory Networks
Humans
Immunoglobulin A
Intestinal Mucosa
Lipid Metabolism
Metagenome
Mice
Mice, Inbred BALB C
Mice, Knockout
Microarray Analysis
Up-Regulation