Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 14.
doi: 10.1097/HEP.0000000000001232. Online ahead of print.

CD44 in myeloid cells is a major driver of liver inflammation and injury in alcohol-associated liver disease

Déborah Rousseau  1 , Stéphanie Bonnafous  2 , Frédéric Soysouvanh  1 , Dorian Sarrail  1 , Manon Bourinet  1 , Axelle Strazzulla  1 , Stéphanie Patouraux  2   3 , Arnaud Borderie  3 , Bastien Dolfi  4 , Alexandre Gallerand  4 , Marwin A Farrugia  2 , Véronique Orian-Rousseau  5 , Yingzheng Xu  6 , Jesse W Williams  6 , Stoyan Ivanov  4 , Albert Tran  2 , Rodolphe Anty  2 , Carmelo Luci  1 , Philippe Gual  1
Affiliations

CD44 in myeloid cells is a major driver of liver inflammation and injury in alcohol-associated liver disease

Déborah Rousseau et al. Hepatology. .

Abstract

Background and aims: Alcohol-associated liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-associated steatohepatitis. CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to alcohol-associated steatohepatitis development in mice and its expression in patients with ALD.

Approach and results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency ( Cd44-/- ) partially protected mice on chronic plus binge ethanol feeding. CD44 deletion in myeloid cells ( Cd44myel-KO ) recapitulated the same protective effects associated with reduced inflammatory monocyte infiltration and neutrophil activation in the liver and diminished blood neutrophil-lymphocyte ratio. CD44-deficient neutrophils displayed reduced phorbol 12-myristate 13-acetate-induced inflammatory mediator expression and increased phagocytosis of live bacteria. Cd44myel-KO mice were also protected against hepatic steatosis mediated by chronic plus binge ethanol feeding or chronic ethanol feeding due in part to increased SIRT1-mediated fatty acid beta-oxidation. CD44 neutralization with antibodies strongly decreased liver injury and inflammation (hepatic neutrophil frequency) and blood neutrophil-lymphocyte ratio on chronic plus binge ethanol feeding. In samples from patients with ALD, hepatic CD44 expression increased with ALD severity, correlated with hepatic TNFα and CD11b expression, and CD44-expressing neutrophils were enriched in alcohol-associated hepatitis.

Conclusions: Human and experimental evidence supports CD44 as a marker of hepatic inflammation in ALD. In addition, CD44 modulates neutrophil mobilization and functions, and its targeting partially prevents liver inflammation and injury in the context of acute-on-chronic alcohol drinking.

Keywords: ALD; alcohol; human; mouse.

PubMed Disclaimer

References

    1. White A, Castle IJ, Chen CM, Shirley M, Roach D, Hingson R. Converging patterns of alcohol use and related outcomes among females and males in the United States, 2002 to 2012. Alcohol Clin Exp Res. 2015;39:1712–1726.
    1. Ntandja Wandji LC, Gnemmi V, Mathurin P, Louvet A. Combined alcoholic and non-alcoholic steatohepatitis. JHEP Rep. 2020;2:100101.
    1. Pruckner N, Hinterbuchinger B, Fellinger M, Konig D, Waldhoer T, Lesch OM, et al. Alcohol-related mortality in the WHO European Region: Sex-specific trends and predictions. Alcohol Alcohol. 2019;54:593–598.
    1. Mathurin P, Bataller R. Trends in the management and burden of alcoholic liver disease. J Hepatol. 2015;62:S38–S46.
    1. Mackowiak B, Fu Y, Maccioni L, Gao B. Alcohol-associated liver disease. J Clin Invest. 2024;134:e176345.

LinkOut - more resources