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Title:
Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut | Nature Medicine
Description:
Polly Matzinger and her colleagues have shown that in the absence of B cells, and in the presence of the microbiota, the intestinal epithelium launches its own immune defense mechanisms. However, this comes at the expense of metabolic programs involved in fat absorption by the gut. These results could explain the lipid malabsorption often seen in humans with common variable immunodeficiency or with HIV infection. 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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nature portfolio permissions reprints privacy policy open mammalian ecosystem intramural research program long-chain acyl-coa synthetase advertising gene expression data open-source nature 444 nature 422 nature social media research gene expression patterns institutional subscriptions read b-lymphocyte development long-term negative effects ifn-induced gtpases mgbp1 osbp-related protein family regulatory cell–iga response tissue-based class control activation-induced cytidine deaminase gut microbiota-derived metabolites mucosal antibody-mediated symbiosis interferon-driven immune dysregulation high-saturated fat diet rebound plasma viremia cytosolic dna-sensing system springerlink instant access permissions present address gut natalia shulzhenko cd79b gene leads systems biology approach core gut microbiome analyzed microbiome data cytokine-producing effector inflammatory bowel disease intestinal th17 cells indigenous intestinal bacteria development epithelial cell growth germ-free mouse privacy governing lipid metabolism immune cell dynamics mucosal immune system intestinal epithelium launches competing financial interests
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- The immune system and the gut microbiota: friends or foes?
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name:Comparative Medicine Branch, NIAID, NIH, Bethesda, USA
name:Immunology Institute, Mount Sinai Medical Center, New York, USA
name:University of Bern, Bern, Switzerland
name:University of Bern, Bern, Switzerland
name:Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
name:Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, USA
name:'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, USA
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