Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice. Academic Article uri icon

abstract

  • 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 IL-17 receptor A (IL-17ra-/-) or pharmacological blockade of IL-17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL-17A positively correlated with the alcohol use in excessive drinkers and was further increased in patients with ALD as compared with healthy individuals. Our data suggest that IL-17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL-17A may provide a novel strategy for treatment of alcohol-induced pathology.

published proceedings

  • JCI Insight

altmetric score

  • 1

author list (cited authors)

  • Xu, J., Ma, H., Liu, X., Rosenthal, S., Baglieri, J., McCubbin, R., ... Kisseleva, T.

citation count

  • 29

complete list of authors

  • Xu, Jun||Ma, Hsiao-Yen||Liu, Xiao||Rosenthal, Sara||Baglieri, Jacopo||McCubbin, Ryan||Sun, Mengxi||Koyama, Yukinori||Geoffroy, Cedric G||Saijo, Kaoru||Shang, Linshan||Nishio, Takahiro||Maricic, Igor||Kreifeldt, Max||Kusumanchi, Praveen||Roberts, Amanda||Zheng, Binhai||Kumar, Vipin||Zengler, Karsten||Pizzo, Donald P||Hosseini, Mojgan||Contet, Candice||Glass, Christopher K||Liangpunsakul, Suthat||Tsukamoto, Hidekazu||Gao, Bin||Karin, Michael||Brenner, David A||Koob, George F||Kisseleva, Tatiana

publication date

  • February 2020