Journal
SCIENCE
Volume 342, Issue 6157, Pages 447-453Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1237910
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Funding
- National Institute of Allergy and Infectious Diseases, NIH [AI61093, AI57653, AI95613, AI96187, AI74378, AI073899, DK072201, AI095245]
- Redes Tematicas de Investigacion Cooperativa en Salud/Fondo Europeo de Desarrollo Regional [RD12/0036/0054]
- ICREA Funding Source: Custom
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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-Fc gamma RIIB 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 kappa B. 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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