Title | Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Shan, M, Gentile, M, Yeiser, JR, A Walland, C, Bornstein, VU, Chen, K, He, B, Cassis, L, Bigas, A, Cols, M, Comerma, L, Huang, B, J Blander, M, Xiong, H, Mayer, L, Berin, C, Augenlicht, LH, Velcich, A, Cerutti, A |
Journal | Science |
Volume | 342 |
Issue | 6157 |
Pagination | 447-53 |
Date Published | 2013 Oct 25 |
ISSN | 1095-9203 |
Keywords | Animals, beta Catenin, Cells, Cultured, Dendritic Cells, Galectin 3, Glycosylation, Homeostasis, Humans, Immune Tolerance, Inflammation, Intestinal Mucosa, Intestine, Small, Lectins, C-Type, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mouth, Mucin-2, Mucus, NF-kappa B, Receptors, IgG, Transcription, Genetic |
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. |
DOI | 10.1126/science.1237910 |
Alternate Journal | Science |
PubMed ID | 24072822 |
PubMed Central ID | PMC4005805 |
Grant List | AI95613 / AI / NIAID NIH HHS / United States AI61093 / AI / NIAID NIH HHS / United States DK072201 / DK / NIDDK NIH HHS / United States R01 AI093577 / AI / NIAID NIH HHS / United States U01 AI095613 / AI / NIAID NIH HHS / United States AI073899 / AI / NIAID NIH HHS / United States AI96187 / AI / NIAID NIH HHS / United States P01 DK072201 / DK / NIDDK NIH HHS / United States R01 AI073899 / AI / NIAID NIH HHS / United States P01 AI061093 / AI / NIAID NIH HHS / United States AI57653 / AI / NIAID NIH HHS / United States AI095245 / AI / NIAID NIH HHS / United States U19 AI096187 / AI / NIAID NIH HHS / United States R01 AI057653 / AI / NIAID NIH HHS / United States R01 AI095245 / AI / NIAID NIH HHS / United States AI74378 / AI / NIAID NIH HHS / United States R01 AI074378 / AI / NIAID NIH HHS / United States R56 AI073899 / AI / NIAID NIH HHS / United States |