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

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Beyaz S., Chung C., Mou H., Bauer-Rowe K. E., Xifaras M. E., Ergin I., ...Daha Fazla

Cell Stem Cell, cilt.28, ss.1922-1941, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.stem.2021.08.007
  • Dergi Adı: Cell Stem Cell
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1922-1941
  • Anahtar Kelimeler: antigen presentation, cancer, diet, high-fat diet, intestinal stem cells, MHC-II, microbiome, obesity
  • Yıldız Teknik Üniversitesi Adresli: Evet

Özet

© 2021 Elsevier Inc.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.