← Search

Omics · study · 2026

CD44 IN MYELOID CELLS IS A MAJOR DRIVER OF LIVER INFLAMMATION AND INJURY IN ALCOHOL-RELATED LIVER DISEASE [CD44_Myelo_KO_Ethanol]

Listed in NCBI GEO

Background and Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH).

Description

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 ASH development in mice and its expression in ALD patients.

Approach and Results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency (Cd44-/-) partially protected mice upon chronic plus binge ethanol feeding (CPB-EtOH). 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 (NLR).

Read the rest (2 more)

CD44-deficient neutrophils displayed reduced PMA-induced inflammatory mediator expression and increased phagocytosis of live bacteria. Cd44myel-KO mice were also protected against hepatic steatosis mediated by CPB-EtOH 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 NLR upon CPB-EtOH.

In samples from ALD patients, 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.

Links

Where it is published

Documentation and papers

Topics

From keywords
Life Sciences
Inferred from text
Disease 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE29574915 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title