Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?

被引:41
作者
Lechuga, Susana [1 ]
Braga-Neto, Manuel B. B. [2 ]
Naydenov, Nayden G. G. [1 ]
Rieder, Florian [1 ,2 ]
Ivanov, Andrei I. I. [1 ]
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Inflammat & Immun, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Digest Dis & Surg Inst, Dept Gastroenterol Hepatol & Nutr, Cleveland, OH USA
基金
美国国家卫生研究院;
关键词
actin cytoskeleton; adherens junctions; colonoids; cytokines; enteroids; epithelial barrier; inflammatory bowel diseases; tight junctions; TIGHT JUNCTION PROTEINS; MYOSIN-II MOTOR; INTERFERON-GAMMA; IN-VITRO; INDUCED INCREASE; ULCERATIVE-COLITIS; HUMAN-COLON; PERMEABILITY; KINASE; EXPRESSION;
D O I
10.3389/fimmu.2023.1108289
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Disruption of the intestinal epithelial barrier is a hallmark of mucosal inflammation. It increases exposure of the immune system to luminal microbes, triggering a perpetuating inflammatory response. For several decades, the inflammatory stimuli-induced breakdown of the human gut barrier was studied in vitro by using colon cancer derived epithelial cell lines. While providing a wealth of important data, these cell lines do not completely mimic the morphology and function of normal human intestinal epithelial cells (IEC) due to cancer-related chromosomal abnormalities and oncogenic mutations. The development of human intestinal organoids provided a physiologically-relevant experimental platform to study homeostatic regulation and disease-dependent dysfunctions of the intestinal epithelial barrier. There is need to align and integrate the emerging data obtained with intestinal organoids and classical studies that utilized colon cancer cell lines. This review discusses the utilization of human intestinal organoids to dissect the roles and mechanisms of gut barrier disruption during mucosal inflammation. We summarize available data generated with two major types of organoids derived from either intestinal crypts or induced pluripotent stem cells and compare them to the results of earlier studies with conventional cell lines. We identify research areas where the complementary use of colon cancer-derived cell lines and organoids advance our understanding of epithelial barrier dysfunctions in the inflamed gut and identify unique questions that could be addressed only by using the intestinal organoid platforms.
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页数:15
相关论文
共 173 条
[91]   TNFα Induces LGR5+Stem Cell Dysfunction In Patients With Crohn's Disease [J].
Lee, Chansu ;
An, Minae ;
Joung, Je -Gun ;
Park, Woong-Yang ;
Chang, Dong Kyung ;
Kim, Young-Ho ;
Hong, Sung Noh .
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 2022, 13 (03) :789-808
[92]   Intestinal Epithelial Responses to IL-17 in Adult Stem Cell-derived Human Intestinal Organoids [J].
Lee, Chnasu ;
Song, Joo Hye ;
Cha, Yeo Eun ;
Chang, Dong Kyung ;
Kim, Young-Ho ;
Hong, Sung Noh .
JOURNAL OF CROHNS & COLITIS, 2022, 16 (12) :1911-1923
[93]   Comparative proteomic analysis of cell lines and scrapings of the human intestinal epithelium [J].
Lenaerts, Kaatje ;
Bouwman, Freek G. ;
Lamers, Wouter H. ;
Renes, Johan ;
Mariman, Edwin C. .
BMC GENOMICS, 2007, 8
[94]   Interleukin-28A maintains the intestinal epithelial barrier function through regulation of claudin-1 [J].
Li, Liangzi ;
Zhou, Chao ;
Li, Teming ;
Xiao, Weidong ;
Yu, Min ;
Yang, Hua .
ANNALS OF TRANSLATIONAL MEDICINE, 2021, 9 (05)
[95]   Determining Intestinal Permeability using Lucifer Yellow in an Apical-Out Enteroid Model [J].
Liebe, Heather ;
Schlegel, Camille ;
Cai, Xue ;
Golubkova, Alena ;
Leiva, Tyler ;
Berry, William L. ;
Hunter, Catherine J. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2022, (185)
[96]   Paneth cell defects in Crohn's disease patients promote dysbiosis [J].
Liu, Ta-Chiang ;
Gurram, Bhaskar ;
Baldridge, Megan T. ;
Head, Richard ;
Vy Lam ;
Luo, Chengwei ;
Cao, Yumei ;
Simpson, Pippa ;
Hayward, Michael ;
Holtz, Mary L. ;
Bousounis, Pavlos ;
Noe, Joshua ;
Lerner, Diana ;
Cabrera, Jose ;
Biank, Vincent ;
Stephens, Michael ;
Huttenhower, Curtis ;
McGovern, Dermot P. B. ;
Xavier, Ramnik J. ;
Stappenbeck, Thaddeus S. ;
Salzman, Nita H. .
JCI INSIGHT, 2016, 1 (08)
[97]   The elusive case of human intraepithelial T cells in gut homeostasis and inflammation [J].
Lutter, Lisanne ;
van Konijnenburg, David P. Hoytema ;
Brand, Eelco C. ;
Oldenburg, Bas ;
van Wijk, Femke .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2018, 15 (10) :637-649
[98]   Mechanism of TNF-α modulation of Caco-2 intestinal epithelial tight junction barrier:: role of myosin light-chain kinase protein expression [J].
Ma, TY ;
Boivin, MA ;
Ye, DM ;
Pedram, A ;
Said, HM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2005, 288 (03) :G422-G430
[99]   TNF-α-induced increase in intestinal epithelial tight junction permeability requires NF-κB activation [J].
Ma, TY ;
Iwamoto, GK ;
Hoa, NT ;
Akotia, V ;
Pedram, A ;
Boivin, MA ;
Said, HM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2004, 286 (03) :G367-G376
[100]   OCCLUDING JUNCTION STRUCTURE-FUNCTION RELATIONSHIPS IN A CULTURED EPITHELIAL MONOLAYER [J].
MADARA, JL ;
DHARMSATHAPHORN, K .
JOURNAL OF CELL BIOLOGY, 1985, 101 (06) :2124-2133