Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis

Beyaz, Semir, Chung, Charlie, Mou, Haiwei, Bauer-Rowe, Khristian E, Xifaras, Michael E, Ergin, Ilgin, Dohnalova, Lenka, Biton, Moshe, Shekhar, Karthik, Eskiocak, Onur, Papciak, Katherine, Ozler, Kadir, Almeqdadi, Mohammad, Yueh, Brian, Fein, Miriam, Annamalai, Damodaran, Valle-Encinas, Eider, Erdemir, Aysegul, Dogum, Karoline, Shah, Vyom, Alici-Garipcan, Aybuke, Meyer, Hannah V, Özata, Deniz M, Elinav, Eran, Kucukural, Alper, Kumar, Pawan, McAleer, Jeremy P, Fox, James G, Thaiss, Christoph A, Regev, Aviv, Roper, Jatin, Orkin, Stuart H, Yilmaz, Ömer H (September 2021) Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis. Cell Stem Cell. ISSN 1934-5909

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.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell diseases & disorders > cancer > cancer types > intestinal cancer
CSHL Authors:	Beyaz, Semir Chung, Charlie Mou, Haiwei Xifaras, Michael E. Ergin, Ilgin Eskiocak, Onur Papciak, Katherine Ozler, Kadir Yueh, Brian Fein, Miriam Shah, Vyom Garipcan, Aybuke Meyer, Hannah V.
Communities:	CSHL labs > Beyaz lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 September 2021
Date Deposited:	17 Sep 2021 13:43
Last Modified:	31 May 2022 20:51
URI:	https://repository.cshl.edu/id/eprint/40351

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