Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.
MHC-II
antigen presentation
cancer
diet
high-fat diet
intestinal stem cells
microbiome
obesity
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
04 11 2021
04 11 2021
Historique:
received:
19
10
2020
revised:
25
05
2021
accepted:
10
08
2021
pubmed:
17
9
2021
medline:
16
11
2021
entrez:
16
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34529935
pii: S1934-5909(21)00344-1
doi: 10.1016/j.stem.2021.08.007
pmc: PMC8650761
mid: NIHMS1742234
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class II
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1922-1935.e5Subventions
Organisme : NCI NIH HHS
ID : R01 CA245314
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126545
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA254314
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA250554
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211184
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing financial interests. S.H.O. serves as an advisory board member for Cell Stem Cell. S.B. received research funding from Elstar Therapeutics and Revitope Oncology for research that is not related to this study.
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