Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals Academic Article uri icon

Overview

MeSH Major

  • Homeostasis
  • Immune Tolerance
  • Intestine, Small
  • Mouth
  • Mucus

abstract

  • 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.

publication date

  • January 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4005805

Digital Object Identifier (DOI)

  • 10.1126/science.1237910

PubMed ID

  • 24072822

Additional Document Info

start page

  • 447

end page

  • 53

volume

  • 342

number

  • 6157