Superfund Research Program
The Role of Reactive Oxygen Species and the Microbiome in Toxicant Induced Liver Fibrosis
Project Leader: David A. Brenner
Co-Investigator: Rohit Loomba
Grant Number: P42ES010337
Funding Period: 2017-2023
Project-Specific Links
- Project Summary
Title: Steatohepatitis progresses to cancer via immunosuppression of HCC directed CD8+ T cells
Accession Number: GSE90497
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE90497
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Array expression profiling by high throughput sequencing
Organism(s): Mus musculus
Summary: We show that chronic inflammation and fibrosis in mice with non-alcoholic fatty liver disease (NASH) is accompanied by accumulation of immunoglobulin A (IgA) positive plasmocytes. These cells suppress activation of cytotoxic T cells (CTL) derived from liver infiltrating CD8+ cells. CD8+ T cell ablation greatly accelerates HCC appearance, genetic or pharmacological targeting of IgA and PD-L1 expressing plasmocytes attenuates hepatic carcinogenesis and induces CTL-dependent regression of established HCC.
Publication(s) associated with this dataset:- Shalapour S, Lin X, Bastian IN, Brain J, Burt AD, Aksenov AA, Vrbanac AF, Li W, Perkins A, Matsutani T, Zhong Z, Dhar D, Navas-Molina JA, Xu J, Loomba R, Downes M, Yu RT, Evans RM, Dorrestein PC, Knight R, Benner CW, Anstee QM, Karin M. 2017. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 551(7680):340-345. doi:10.1038/nature24302 PMID:29144460 PMCID:PMC5884449