Publication

Expression of AXL receptor tyrosine kinase relates to monocyte dysfunction and severity of cirrhosis

Journal Paper/Review - Dec 10, 2019

Units
PubMed
Doi

Citation
Brenig R, Antoniades C, Wendon J, Heim M, Ludewig B, Weston C, Duong F, Semela D, Brand S, Boldanova T, Künzler-Heule P, Cupovic J, Besse L, Pérez Shibayama C, Singanayagam A, Geng A, Triantafyllou E, Pop O, Bernsmeier C. Expression of AXL receptor tyrosine kinase relates to monocyte dysfunction and severity of cirrhosis. Life Sci Alliance 2019; 3
Type
Journal Paper/Review (English)
Journal
Life Sci Alliance 2019; 3
Publication Date
Dec 10, 2019
Issn Electronic
2575-1077
Brief description/objective

Infectious complications in patients with cirrhosis frequently initiate episodes of decompensation and substantially contribute to the high mortality. Mechanisms of the underlying immuneparesis remain underexplored. TAM receptors (TYRO3/AXL/MERTK) are important inhibitors of innate immune responses. To understand the pathophysiology of immuneparesis in cirrhosis, we detailed TAM receptor expression in relation to monocyte function and disease severity prior to the onset of acute decompensation. TNF-α/IL-6 responses to lipopolysaccharide were attenuated in monocytes from patients with cirrhosis (n = 96) compared with controls (n = 27) and decreased in parallel with disease severity. Concurrently, an AXL-expressing (AXL) monocyte population expanded. AXL cells (CD14CD16HLA-DR) were characterised by attenuated TNF-α/IL-6 responses and T cell activation but enhanced efferocytosis and preserved phagocytosis of Their expansion correlated with disease severity, complications, infection, and 1-yr mortality. AXL monocytes were generated in response to microbial products and efferocytosis in vitro. AXL kinase inhibition and down-regulation reversed attenuated monocyte inflammatory responses in cirrhosis ex vivo. AXL may thus serve as prognostic marker and deserves evaluation as immunotherapeutic target in cirrhosis.