Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals

Meimei Shan, Maurizio Gentile, John R. Yeiser, A. Cooper Walland, Victor U. Bornstein, Kang Chen, Bing He, Linda Cassis, Anna Bigas, Montserrat Cols, Laura Comerma, Bihui Huang, J. Magarian Blander, Huabao Xiong, Lloyd Mayer, Cecilia Berin, Leonard H. Augenlicht, Anna Velcich, Andrea Cerutti

Research output: Contribution to journalArticle

245 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalScience
Volume342
Issue number6157
DOIs
StatePublished - 2013

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Mucus
Homeostasis
Dendritic Cells
Antigens
Galectin 3
Catenins
Architectural Accessibility
Large Intestine
Mucins
Small Intestine
Polysaccharides
Anti-Inflammatory Agents
Transcription Factors
Epithelium
Epithelial Cells
Cytokines
Inflammation
Bacteria
Food
Genes

ASJC Scopus subject areas

  • General

Cite this

Shan, M., Gentile, M., Yeiser, J. R., Walland, A. C., Bornstein, V. U., Chen, K., ... Cerutti, A. (2013). Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science, 342(6157), 447-453. https://doi.org/10.1126/science.1237910

Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. / Shan, Meimei; Gentile, Maurizio; Yeiser, John R.; Walland, A. Cooper; Bornstein, Victor U.; Chen, Kang; He, Bing; Cassis, Linda; Bigas, Anna; Cols, Montserrat; Comerma, Laura; Huang, Bihui; Blander, J. Magarian; Xiong, Huabao; Mayer, Lloyd; Berin, Cecilia; Augenlicht, Leonard H.; Velcich, Anna; Cerutti, Andrea.

In: Science, Vol. 342, No. 6157, 2013, p. 447-453.

Research output: Contribution to journalArticle

Shan, M, Gentile, M, Yeiser, JR, Walland, AC, Bornstein, VU, Chen, K, He, B, Cassis, L, Bigas, A, Cols, M, Comerma, L, Huang, B, Blander, JM, Xiong, H, Mayer, L, Berin, C, Augenlicht, LH, Velcich, A & Cerutti, A 2013, 'Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals', Science, vol. 342, no. 6157, pp. 447-453. https://doi.org/10.1126/science.1237910
Shan M, Gentile M, Yeiser JR, Walland AC, Bornstein VU, Chen K et al. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science. 2013;342(6157):447-453. https://doi.org/10.1126/science.1237910
Shan, Meimei ; Gentile, Maurizio ; Yeiser, John R. ; Walland, A. Cooper ; Bornstein, Victor U. ; Chen, Kang ; He, Bing ; Cassis, Linda ; Bigas, Anna ; Cols, Montserrat ; Comerma, Laura ; Huang, Bihui ; Blander, J. Magarian ; Xiong, Huabao ; Mayer, Lloyd ; Berin, Cecilia ; Augenlicht, Leonard H. ; Velcich, Anna ; Cerutti, Andrea. / Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. In: Science. 2013 ; Vol. 342, No. 6157. pp. 447-453.
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