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Publication : Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals.

First Author  Shan M Year  2013
Journal  Science Volume  342
Issue  6157 Pages  447-53
PubMed ID  24072822 Mgi Jnum  J:202829
Mgi Id  MGI:5522591 Doi  10.1126/science.1237910
Citation  Shan M, et al. (2013) Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342(6157):447-53
abstractText  A dense mucus layer in the large intestine prevents inflammation by shielding the underlying epithelium from luminal bacteria and food antigens. This mucus barrier is organized around the hyperglycosylated mucin MUC2. Here we show that the small intestine has a porous mucus layer, which permitted the uptake of MUC2 by antigen-sampling dendritic cells (DCs). Glycans associated with MUC2 imprinted DCs with anti-inflammatory properties by assembling a galectin-3-Dectin-1-FcgammaRIIB receptor complex that activated beta-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor kappaB. MUC2 induced additional conditioning signals in intestinal epithelial cells. Thus, mucus does not merely form a nonspecific physical barrier, but also constrains the immunogenicity of gut antigens by delivering tolerogenic signals.
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