Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis
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,...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2023
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| Online Access: | https://hdl.handle.net/1721.1/147038 |
| _version_ | 1826191931033518080 |
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| author | Yilmaz, Omer |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yilmaz, Omer |
| author_sort | Yilmaz, Omer |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:03:34Z |
| format | Article |
| id | mit-1721.1/147038 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:03:34Z |
| publishDate | 2023 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1470382023-01-11T03:43:51Z Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis Yilmaz, Omer Massachusetts Institute of Technology. Department of Biology 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. 2023-01-10T17:16:21Z 2023-01-10T17:16:21Z 2021 2023-01-10T17:10:05Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147038 Yilmaz, Omer. 2021. "Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis." Cell Stem Cell, 28 (11). en 10.1016/J.STEM.2021.08.007 Cell Stem Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Yilmaz, Omer Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title | Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title_full | Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title_fullStr | Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title_full_unstemmed | Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title_short | Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| title_sort | dietary suppression of mhc class ii expression in intestinal epithelial cells enhances intestinal tumorigenesis |
| url | https://hdl.handle.net/1721.1/147038 |
| work_keys_str_mv | AT yilmazomer dietarysuppressionofmhcclassiiexpressioninintestinalepithelialcellsenhancesintestinaltumorigenesis |