Mucus Enhances Gut Homeostasis and Oral Tolerance by Delivering Immunoregulatory Signals

作者：Meimei Shan, Maurizio Gentile, John R. Yeiser, Alexander Walland, Victor Ugarte Bornstein, Kang Chen, Bing He, Linda Cassis, Anna Bigas, Montserrat Cols, Laura Comerma, Bihui Huang, Julie Magarian Blander, Huabao Xiong, Lloyd Mayer, M. Cecilia Berin, Leonard H. Augenlicht, Anna Velcich, Andrea Cerutti · 发表于：Science · 年份：2013 · DOI：10.1126/science.1237910 · 被引用次数：640 · 研究领域：Galectins and Cancer Biology、Glycosylation and Glycoproteins Research、Immune Cell Function and Interaction

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.