美国麻省理工学院Ömer H. Yilmaz等研究人员合作发现，饮食对肠道上皮细胞MHC II类表达的抑制会增强肠道肿瘤的发生。2021年9月15日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员表明，高脂肪饮食（HFD）减少了肠道上皮细胞（包括肠道干细胞ISC）中主要组织相容性复合体II类（MHC II类）基因的表达。HFD中上皮细胞MHC II类基因表达的这种下降与肠道微生物群多样性的减少有关。微生物群落转移实验表明，上皮细胞MHC II类的表达受肠道菌群的调节。

机制上，模式识别受体（PRR）和干扰素-γ（IFNγ）信号调节上皮MHC II类的表达。在失去肿瘤抑制因子Apc后，再加上HFD，MHC II类阴性（MHC-II-）的ISC比MHC II类阳性（MHC-II+）的ISC显示出更强的肿瘤起始能力，这提示了上皮MHC II类介导的免疫监视在抑制肿瘤发生中的作用。ISC特异性的MHC II基因敲除会自主地增加肿瘤负担细胞。因此，HFD扰乱了微生物群-干细胞-免疫细胞的相互作用，从而有助于肠道内肿瘤的发生。

据了解，对于饮食、ISC和免疫细胞的相互作用如何影响早期肠道肿瘤的发生知之甚少。

附：英文原文

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

Author: Semir Beyaz, Charlie Chung, Haiwei Mou, Khristian E. Bauer-Rowe, Michael E. Xifaras, Ilgin Ergin, Lenka Dohnalova, Moshe Biton, Karthik Shekhar, Onur Eskiocak, Katherine Papciak, Kadir Ozler, Mohammad Almeqdadi, Brian Yueh, Miriam Fein, Damodaran Annamalai, Eider Valle-Encinas, Aysegul Erdemir, Karoline Dogum, Vyom Shah, Aybuke Alici-Garipcan, Hannah V. Meyer, Deniz M. zata, Eran Elinav, Alper Kucukural, Pawan Kumar, Jeremy P. McAleer, James G. Fox, Christoph A. Thaiss, Aviv Regev, Jatin Roper, Stuart H. Orkin, mer H. Yilmaz

Issue&Volume: 2021-09-15

Abstract: Little is known about how interactions of diet, intestinal stem cells (ISCs), andimmune cells affect early-stage intestinal tumorigenesis. We show that a high-fatdiet (HFD) reduces the expression of the major histocompatibility complex class II(MHC class II) genes in intestinal epithelial cells, including ISCs. This declinein epithelial MHC class II expression in a HFD correlates with reduced intestinalmicrobiome diversity. Microbial community transfer experiments suggest that epithelialMHC class II expression is regulated by intestinal flora. Mechanistically, patternrecognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelialMHC class II expression. MHC class II-negative (MHC-II) ISCs exhibit greater tumor-initiatingcapacity than their MHC class II-positive (MHC-II+) counterparts upon loss of thetumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC classII-mediated immune surveillance in suppressing tumorigenesis. ISC-specific geneticablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbsa microbiome-stem cell-immune cell interaction that contributes to tumor initiationin the intestine.

DOI: 10.1016/j.stem.2021.08.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00344-1