University of Massachusetts Medical School Faculty Publications
Title
Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis
UMMS Affiliation
RNA Therapeutics Institute; Program in Molecular Medicine
Publication Date
2021-11-04
Document Type
Article
Disciplines
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
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 (IFNgamma) 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.
Keywords
MHC-II, antigen presentation, cancer, diet, high-fat diet, intestinal stem cells, microbiome, obesity
DOI of Published Version
10.1016/j.stem.2021.08.007
Source
Beyaz S, Chung C, Mou H, Bauer-Rowe KE, Xifaras ME, Ergin I, Dohnalova L, Biton M, Shekhar K, Eskiocak O, Papciak K, Ozler K, Almeqdadi M, Yueh B, Fein M, Annamalai D, Valle-Encinas E, Erdemir A, Dogum K, Shah V, Alici-Garipcan A, Meyer HV, Özata DM, Elinav E, Kucukural A, Kumar P, McAleer JP, Fox JG, Thaiss CA, Regev A, Roper J, Orkin SH, Yilmaz ÖH. Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell. 2021 Nov 4;28(11):1922-1935.e5. doi: 10.1016/j.stem.2021.08.007. Epub 2021 Sep 15. PMID: 34529935; PMCID: PMC8650761. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Cell stem cell
PubMed ID
34529935
Repository Citation
Beyaz S, Chung C, Mou H, Bauer-Rowe KE, Xifaras ME, Ergin I, Dohnalova L, Biton M, Shekhar K, Eskiocak O, Papciak K, Ozler K, Almeqdadi M, Yueh B, Fein M, Annamalai D, Valle-Encinas E, Erdemir A, Dogum K, Shah V, Alici-Garipcan A, Meyer HV, Ozata DM, Elinav E, Kucukural A, Kumar P, McAleer JP, Fox JG, Thaiss CA, Regev A, Roper J, Orkin SH, Yilmaz OH. (2021). Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1016/j.stem.2021.08.007. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2116