TY - JOUR T1 - Expression of AXL receptor tyrosine kinase relates to monocyte dysfunction and severity of cirrhosis JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900465 VL - 3 IS - 1 SP - e201900465 AU - Robert Brenig AU - Oltin T Pop AU - Evangelos Triantafyllou AU - Anne Geng AU - Arjuna Singanayagam AU - Christian Perez-Shibayama AU - Lenka Besse AU - Jovana Cupovic AU - Patrizia Künzler AU - Tuyana Boldanova AU - Stephan Brand AU - David Semela AU - François HT Duong AU - Christopher J Weston AU - Burkhard Ludewig AU - Markus H Heim AU - Julia Wendon AU - Charalambos G Antoniades AU - Christine Bernsmeier Y1 - 2020/01/01 UR - https://www.life-science-alliance.org/content/3/1/e201900465.abstract N2 - 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. ER -