ArticleCell stem cell2021
Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.
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Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94citing papers in PubMed
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Who cites it
94 citing papers in PubMed, 134 citations in OpenAlex.
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
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- Dietary Regulation of Intestinal Stem Cell Function: Nutrient-Sensing, Microbiota-Mediated, and Regenerative Mechanisms from a Dietetic Perspective.Biomedicines · 2026Review
- Intestinal Epithelial MHC-II at the Interface of Microbiota, Immunity, and Inflammation.International journal of molecular sciences · 2026Review
- Human pancreatic ductal cells from non-diabetic donors function as non-professional antigen-presenting cells upon inflammatory cytokine exposure.Diabetologia · 2026Article
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- Curcumin-loaded tetrahedral framework nucleic acids reshape intestinal homeostasis in ulcerative colitis by coordinating barrier repair, microbiota reconstruction, and immune modulation.Materials today. Bio · 2026Article
- Colorectal cancers with distinct metastatic potential trigger divergent early T cell responses.bioRxiv : the preprint server for biology · 2026Article
- Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis.bioRxiv : the preprint server for biology · 2026Article
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Lacticaseibacillus casei Zhang modulates iron homeostasis in iron-overloaded mice via an IL-22-dependent pathways.NPJ science of food · 2026Article
- Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity.Cancer cell · 2026Article
- Diverse high-fat diets drive multi-omic reprogramming that persists after dietary reversal.bioRxiv : the preprint server for biology · 2026Article
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- Weaning drives microbiome-mediated epigenetic regulation to shape immune memory in mice.Nature microbiology · 2026Article
- Article
- Ancestrally Diverse Autologous Patient-Derived Organoid-Immune Cell Coculture Platform for Addressing Immunotherapeutic Outcome Disparities in High-Grade Endometrial Cancer.Cancer research communications · 2026Article
- Diet-induced chromatin states influence intestinal stem cell memory.bioRxiv : the preprint server for biology · 2026Article
- Oesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an IFNγ-Dependent Manner.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Rejuvenating the aging gut by targeting senescence.Nature aging · 2026Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 13 institutions in 2 countries.
Semir BeyazCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA. Electronic address: beyaz@cshl.edu.
Charlie ChungCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Haiwei MouCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Khristian E Bauer-RoweThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Michael E XifarasCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Ilgin ErginCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Lenka DohnalovaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Moshe BitonKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; The Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
Karthik ShekharKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemical and Biomolecular Engineering, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
Onur EskiocakCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Katherine PapciakCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Kadir OzlerCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Mohammad AlmeqdadiThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Brian YuehCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Miriam FeinCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Damodaran AnnamalaiDivision of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Eider Valle-EncinasThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Aysegul ErdemirThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Karoline DogumThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
Vyom ShahCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Aybuke Alici-GaripcanCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Hannah V MeyerCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Deniz M ÖzataRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Eran ElinavDepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Alper KucukuralProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Pawan KumarDepartment of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Jeremy P McAleerDepartment of Pharmaceutical Science and Research, Marshall University School of Pharmacy, Huntington, WV 25701, USA.
James G FoxDivision of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Christoph A ThaissDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aviv RegevThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
Jatin RoperDepartment of Medicine, Division of Gastroenterology, Duke University, Durham, NC 27710, USA.
Stuart H OrkinDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: stuart_orkin@dfci.harvard.edu.
Ömer H YilmazThe David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: ohyilmaz@mit.edu.
Cold Spring Harbor Laboratory · USKoch Institute for Integrative Cancer Research At MITHarvard University · USMassachusetts Institute of Technology · USUniversity of Massachusetts Chan Medical School · USUniversity of Pennsylvania · USWeizmann Institute of Science · ILBroad Institute · USDuke University · USHoward Hughes Medical Institute · USMarshall University · USMassachusetts General Hospital · USStony Brook University · US
Funding
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8MSingle-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9MPilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3MMechanisms of HIV-associated epithelialintestinal stem cell (ISC) dysfunctionR01DK126545 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KLOVERPRIS, HENRIK, KWON, DOUGLAS · 2020 to 2024
$3.6MDeveloping high-throughput genetic perturbation strategies for single cells in cancer organoidsU01CA250554 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERGER, BONNIE, YILMAZ, OMER · 2020 to 2022
$2.8MImpact of fasting on intestinal stem cells and cancerR01CA245314 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Omer Yilmaz · 2020 to 2026
$2.3MDietary control of stem cells in physiology and cancerR01CA211184 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 2017 to 2021
$2.0MOptimizing Gram-positive bacteria as a candidate for targeted anti-tumor therapyF32CA254314 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SHUSTER, BENTLEY M. · 2020 to 2022
$151kHoward Hughes Medical InstituteNCI NIH HHS F32 CA254314NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA045508NCI NIH HHS R01 CA211184NCI NIH HHS R01 CA245314NCI NIH HHS U01 CA250554NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK126545
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.
Indexed as
Histocompatibility Antigens Class IIIntestinesCarcinogenesisDiet, High-FatEpithelial CellsHumansHistocompatibility Antigens Class IIantigen presentationcancerdiethigh-fat dietintestinal stem cellsMHC-IImicrobiomeobesity
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