Title: Blockade of lL17 signaling reverses alcohol-induced liver injury, and excessive alcohol drinking in mice.

Accession Number: GSE137228

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137228

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL17 Receptor A (IL17ra-/-), or pharmacological blockade of IL17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice, and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL17A positively correlated with the alcohol use in excessive drinkers, and was further increased in patients with ALD as compared to healthy individuals. Our data suggest that IL17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL17A may provide a novel strategy for treatment of alcohol-induced pathology.

Publication(s) associated with this dataset:

• Xu J, Ma H, Liu X, Rosenthal SB, Baglieri J, Mccubbin R, Sun M, Koyama Y, Geoffroy C, Saijo K, Shang L, Nishio T, Maricic I, Kriefeldt M, Kusumanchi P, Roberts a, Zheng B, Kumar V, Zengler K, Pizzo D, Hosseini M, Contet C, Glass CK, Liangpunsakul S, Tsukamoto H, Gao B, Karin M, Brenner DA, Koob G, Kisseleva T. 2020. Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice. JCI Insight doi:10.1172/jci.insight.131277 PMID:32051339 PMCID:PMC7098802