Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis
Copyright © 2021 Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Nat Rev Immunol. 2021 Nov;21(11):692-693. - PMID 34535786 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Cell stem cell - 28(2021), 11 vom: 04. Nov., Seite 1922-1935.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Beyaz, Semir [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.11.2021 Date Revised 05.11.2022 published: Print-Electronic CommentIn: Nat Rev Immunol. 2021 Nov;21(11):692-693. - PMID 34535786 Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2021.08.007 |
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| PPN (Katalog-ID): |
NLM330719122 |
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| 245 | 1 | 0 | |a Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis |
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| 500 | |a CommentIn: Nat Rev Immunol. 2021 Nov;21(11):692-693. - PMID 34535786 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MHC-II | |
| 650 | 4 | |a antigen presentation | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a diet | |
| 650 | 4 | |a high-fat diet | |
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| 650 | 4 | |a microbiome | |
| 650 | 4 | |a obesity | |
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