title: Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut.
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.
authors.affiliation: '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
authors.forename: Natalia
authors.initials: N
authors.lastname: Shulzhenko
authors.forename: Andrey
authors.initials: A
authors.lastname: Morgun
authors.forename: William
authors.initials: W
authors.lastname: Hsiao
authors.forename: Michele
authors.initials: M
authors.lastname: Battle
authors.forename: Michael
authors.initials: M
authors.lastname: Yao
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Marlene
authors.initials: M
authors.lastname: Orandle
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Macpherson
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.forename: Claire
authors.initials: C
authors.lastname: Fraser-Liggett
authors.forename: Polly
authors.initials: P
authors.lastname: Matzinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004269:DNA, Bacterial / Q000302:isolation & purification; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D050356:Lipid Metabolism; D054892:Metagenome; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D046228:Microarray Analysis; D015854:Up-Regulation
chemical_list: D004269:DNA, Bacterial; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D007070:Immunoglobulin A
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