Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis
Name
nihms-1742234.pdf
Description
Accepted version
Size
3.71 MB
Format
Adobe PDF
Checksum (MD5)
3c6d85dbc86edde82dc62033665393ee
Author(s)
Yilmaz, Omer
Date Issued
2021
Journal
Cell Stem Cell
Publisher
Elsevier BV
Citation
Yilmaz, Omer. 2021. "Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis." Cell Stem Cell, 28 (11).
Version
Author's final manuscript
Abstract
Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1016/J.STEM.2021.08.007
