Imperial College London
Alternate

ProfessorIanWilson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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i.wilson

 
 
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Location

 

311Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Triantafyllou:2017:10.1136/gutjnl-2016-313615,
author = {Triantafyllou, E and Pop, O and Possamai, L and Wilhelm, A and Liaskou, E and Singanayagam, A and Bernsmeier, C and Khamri, W and Petts, G and Dargue, R and Davies, S and Tickle, J and Yuksel, M and Patel, V and Abeles, R and Stamataki, Z and Curbishley, S and Ma, Y and Wilson, I and Coen, M and Woollard, K and Quaglia, A and Wendon, J and Thursz, M and Adams, D and Weston, C and Antoniades, C},
doi = {10.1136/gutjnl-2016-313615},
journal = {Gut},
pages = {333--347},
title = {MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure},
url = {http://dx.doi.org/10.1136/gutjnl-2016-313615},
volume = {67},
year = {2017}
}
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TY  - JOUR
AB  - Objective Acute liver failure (ALF) is characterised by overwhelming hepatocyte death and liver inflammation with massive infiltration of myeloid cells in necrotic areas. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown. Here, we aimed to investigate the impact of Mer tyrosine kinase (MerTK) during ALF and also examine how the microenvironmental mediator, secretory leucocyte protease inhibitor (SLPI), governs this response.Design Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotype, functional/transcriptomic profile and tissue topography of MerTK+ monocytes/macrophages in ALF, healthy and disease controls. The temporal evolution of macrophage MerTK expression and its impact on resolution was examined in APAP-induced acute liver injury using wild-type (WT) and Mer-deficient (Mer−/−) mice. SLPI effects on hepatic myeloid cells were determined in vitro and in vivo using APAP-treated WT mice.Results We demonstrate a significant expansion of resolution-like MerTK+HLA-DRhigh cells in circulatory and tissue compartments of patients with ALF. Compared with WT mice which show an increase of MerTK+MHCIIhigh macrophages during the resolution phase in ALF, APAP-treated Mer−/− mice exhibit persistent liver injury and inflammation, characterised by a decreased proportion of resident Kupffer cells and increased number of neutrophils. Both in vitro and in APAP-treated mice, SLPI reprogrammes myeloid cells towards resolution responses through induction of a MerTK+HLA-DRhigh phenotype which promotes neutrophil apoptosis and their subsequent clearance.Conclusions We identify a hepatoprotective, MerTK+, macrophage phenotype that evolves during the resolution phase following ALF and represents a novel immunotherapeutic target to promote resolution responses following acute liver injury.
AU  - Triantafyllou,E
AU  - Pop,O
AU  - Possamai,L
AU  - Wilhelm,A
AU  - Liaskou,E
AU  - Singanayagam,A
AU  - Bernsmeier,C
AU  - Khamri,W
AU  - Petts,G
AU  - Dargue,R
AU  - Davies,S
AU  - Tickle,J
AU  - Yuksel,M
AU  - Patel,V
AU  - Abeles,R
AU  - Stamataki,Z
AU  - Curbishley,S
AU  - Ma,Y
AU  - Wilson,I
AU  - Coen,M
AU  - Woollard,K
AU  - Quaglia,A
AU  - Wendon,J
AU  - Thursz,M
AU  - Adams,D
AU  - Weston,C
AU  - Antoniades,C
DO  - 10.1136/gutjnl-2016-313615
EP  - 347
PY  - 2017///
SN  - 1468-3288
SP  - 333
TI  - MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure
T2  - Gut
UR  - http://dx.doi.org/10.1136/gutjnl-2016-313615
UR  - http://hdl.handle.net/10044/1/46258
VL  - 67
ER  -
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