TY - JOUR
T1 - Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals
AU - Shan, Meimei
AU - Gentile, Maurizio
AU - Yeiser, John R.
AU - Walland, A. Cooper
AU - Bornstein, Victor U.
AU - Chen, Kang
AU - He, Bing
AU - Cassis, Linda
AU - Bigas, Anna
AU - Cols, Montserrat
AU - Comerma, Laura
AU - Huang, Bihui
AU - Blander, J. Magarian
AU - Xiong, Huabao
AU - Mayer, Lloyd
AU - Berin, Cecilia
AU - Augenlicht, Leonard H.
AU - Velcich, Anna
AU - Cerutti, Andrea
PY - 2013
Y1 - 2013
N2 - 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-FcγRIIB receptor complex that activated β-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor κB. 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.
AB - 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-FcγRIIB receptor complex that activated β-catenin. This transcription factor interfered with DC expression of inflammatory but not tolerogenic cytokines by inhibiting gene transcription through nuclear factor κB. 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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UR - http://www.scopus.com/inward/citedby.url?scp=84886280379&partnerID=8YFLogxK
U2 - 10.1126/science.1237910
DO - 10.1126/science.1237910
M3 - Article
C2 - 24072822
AN - SCOPUS:84886280379
SN - 0036-8075
VL - 342
SP - 447
EP - 453
JO - Science
JF - Science
IS - 6157
ER -