Intestinal iNKT cells migrate to liver and contribute to hepatocyte apoptosis during alcoholic liver disease

American Journal of Physiology. Gastrointestinal and Liver Physiology
Kuei-Chuan LeeBernd Schnabl

Abstract

We investigated the migration of intestinal immune cells to the liver and their contribution to alcoholic liver disease. In mice fed ethanol, we found that an increased number of invariant natural killer T (iNKT) cells, which respond to the antigen presented by CD1d, migrated from mesenteric lymph nodes to the liver. iNKT cells react to lipid antigens, so we studied their activities in mice with intestinal epithelial cell-specific deletion of Pparg (PpargΔIEC) as a model for altering intestinal lipidomic profiles. Levels of CD1d increased in intestines of ethanol-fed PpargΔIEC mice, and in cell-tracking experiments, more iNKT cells migrated to the liver, compared with mice without disruption of Pparg. Livers of PpargΔIEC mice had increased markers of apoptosis and liver injury after ethanol feeding. iNKT cells isolated from livers of ethanol-fed PpargΔIEC mice induced apoptosis of cultured hepatocytes. An inhibitor of iNKT cells reduced ethanol-induced liver injury in PpargΔIEC mice. Duodenal tissues from patients with alcohol-use disorder have been found to have increased levels of CD1d compared with tissues from patients without alcohol overuse. Ethanol use, therefore, activates iNKT cells in the intestine to migrate to liver...Continue Reading

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Citations

Mar 11, 2020·Alcoholism, Clinical and Experimental Research·Idania MarreroVipin Kumar
May 14, 2020·Cells·Weili XuAnis Larbi
Oct 13, 2020·Cellular & Molecular Immunology·Yongyan Chen, Zhigang Tian
Dec 4, 2020·Cellular & Molecular Immunology·Hua WangYaron Rotman
Jan 29, 2021·BioMed Research International·Jun GuanHaihong Zhu
Jan 10, 2021·Journal of Digestive Diseases·Jian GanJun Feng Li
Jun 5, 2021·Cellular and Molecular Gastroenterology and Hepatology·Yun-Cheng HsiehHan-Chieh Lin
Jul 11, 2021·Trends in Immunology·Stephanie C EisenbarthMichelle A Linterman

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Methods Mentioned

BETA
flow cytometry
fluorescence-activated cell sorting
PCR
ELISA
biopsies
transgenic

Software Mentioned

GraphPad Prism
Progenesis QI
GraphPad
R
EZinfo
MassLynx

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