King's College London

Research portal

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

Research output: Contribution to journalArticle

Robert Brenig, Oltin T. Pop, Evangelos Triantafyllou, Anne Geng, Arjuna Singanayagam, Christian Perez-Shibayama, Lenka Besse, Jovana Cupovic, Patrizia Künzler, Tuyana Boldanova, Stephan Brand, David Semela, François Ht Duong, Christopher J. Weston, Burkhard Ludewig, Markus H. Heim, Julia Wendon, Charalambos G. Antoniades, Christine Bernsmeier

Original languageEnglish
Article numbere201900465
JournalLife Science Alliance
Volume3
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

King's Authors

Abstract

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 (CD14+CD16highHLA-DRhigh) were characterised by attenuated TNF-α/IL-6 responses and T cell activation but enhanced efferocytosis and preserved phagocytosis of Escherichia coli 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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454