The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure

Abhishek Chauhan*, Lozan Sheriff, Mohammed T Hussain, Gwilym J Webb, Daniel A Patten, Emma Louise Shepherd, Robert K Shaw, Christopher J Weston, Debashis Haldar, Samuel Bourke, Rajan Bhandari, Stephanie Watson, David H. Adams, Steve P. Watson, Patricia F. Lalor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.

Original languageEnglish
Article number1939
Number of pages12
JournalNature Communications
Issue number1
Publication statusPublished - 22 Apr 2020

Bibliographical note

© The Author(s) 2020 This article is licensed under a Creative Commons Attribution 4.0 International License, to view a copy of this license, visit


  • Acetaminophen/adverse effects
  • Animals
  • Blood Platelets/immunology
  • Carbon Tetrachloride/adverse effects
  • Chemical and Drug Induced Liver Injury/etiology
  • Humans
  • Lectins, C-Type/genetics
  • Liver/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils/immunology
  • Tumor Necrosis Factor-alpha/genetics


Dive into the research topics of 'The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure'. Together they form a unique fingerprint.

Cite this