Dietary modulation of GALT.
Changes in diet greatly affect the mucosal immune system, particularly in diseases such as Crohn's disease and necrotizing enterocolitis. This article examines the hypothesis that alterations in the luminal environment of the intestine regulate the expression of genes in the enterocyte responsible for signaling to immune cells. Genes expressed by the epithelium orchestrate leukocytes in the lamina propria. For example, chemokine expression in the mouse intestinal epithelium, through transgenic means, induced the recruitment of neutrophils and lymphocytes into intestinal tissues. Diet alters the expression of the genes responsible for signaling by a variety of pathways. The introduction of a normal diet to a weanling mouse up-regulates MHC class II expression through a particular isoform of the class II transactivator, a protein that acts in the nucleus. SCFA concentrations in the intestinal lumen vary markedly with diet. SCFAs increase IL-8 and insulin-like growth factor binding protein-2 expression by inhibiting histone deacetylase activity in the enterocyte. Down-regulation of gene expression by butyrate can act through acetylation of the inhibitory transcription factor Sp3. The review therefore describes a number of molecular pathways, explaining how changes in diet may alter leukocyte recruitment by regulating enterocyte gene expression. Myofibroblasts enhance enterocyte chemotactic activity by cleaving inactive precursors; and myofibroblast genes also are regulated by SCFA. It is likely that other similar regulatory mechanisms remain to be discovered.
Sanderson
Ian R
IR
Research Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK. i.r.sanderson@qmul.ac.uk
D000818:Animals; D004032:Diet; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007444:Inulin / Q000008:administration & dosage / Q000494:pharmacology*; D009844:Oligosaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D005232:Fatty Acids, Volatile; D009844:Oligosaccharides; C120489:oligofructose; D007444:Inulin