Imperial College London
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Dr Evangelos Triantafyllou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Lecturer in Liver Immunology
 
 
 
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Contact

 

e.triantafyllou Website

 
 
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Location

 

10.N12ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Trovato:2023:10.1016/j.jhep.2022.10.031,
author = {Trovato, FM and Zia, R and Artru, F and Mujib, S and Jerome, E and Cavazza, A and Coen, M and Wilson, I and Holmes, E and Morgan, P and Singanayagam, A and Bernsmeier, C and Napoli, S and Bernal, W and Wendon, J and Miquel, R and Menon, K and Patel, VC and Smith, J and Atkinson, SR and Triantafyllou, E and McPhail, MJ},
doi = {10.1016/j.jhep.2022.10.031},
journal = {Journal of Hepatology},
pages = {558--573},
title = {Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure.},
url = {http://dx.doi.org/10.1016/j.jhep.2022.10.031},
volume = {78},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND AND AIMS: Acute liver failure (ALF) is a life-threatening disease characterised by high-grade inflammation and immunoparesis with a high incidence of death from sepsis. Here, we aimed to describe the metabolic dysregulation in ALF and determine whether systemic immune responses are modulated via the lysophosphatidylcholine(LPC)-autotaxin(ATX)-lysophosphatidylcholinic acid (LPA) pathway. METHODS: 96 ALF patients, 71 healthy controls (HC), 104 patients with cirrhosis and 31 septic patients were recruited. The pathways of interest were identified based on multivariate statistical analysis of proton nuclear magnetic resonance (1HNMR) spectroscopy, untargeted ultraperformance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics and validated with a targeted metabolomics panel. Peripheral blood mononuclear cells were cultured with LPA 16:0, 18:0, 18:1, and their immune checkpoint surface expression was assessed by flow cytometry. LPA receptor (LPAR) transcript-level expression of monocytes was investigated and the effect of LPAR antagonism was also examined in vitro. RESULTS: LPC 16:0 was found highly discriminant between ALF and HC. There was an increase in ATX and LPA in ALF compared to HC and sepsis. LPCs 16:0, 18:0 and 18:1 were reduced in ALF patients with poor prognosis. Treatment of monocytes with LPA 16:0 increased their PD-L1 expression and reduced CD155, CD163, MerTK levels, without effect on T and NK/CD56+T cells immune checkpoints. LPAR1 and 3 antagonism in culture reversed the LPA effect on monocyte expression of MerTK and CD163. MerTK and CD163, but not LPARs genes, were differently expressed and upregulated in monocytes from ALF patients compared to controls. CONCLUSION: Reduced amounts of LPCs are biomarkers of poor prognosis in patients with ALF. The LPC-ATX-LPA axis appears to modulate innate immune response in ALF via LPAR1 and LPAR3. Further investigations are required to identify novel therapeutic agents targeting these recept
AU  - Trovato,FM
AU  - Zia,R
AU  - Artru,F
AU  - Mujib,S
AU  - Jerome,E
AU  - Cavazza,A
AU  - Coen,M
AU  - Wilson,I
AU  - Holmes,E
AU  - Morgan,P
AU  - Singanayagam,A
AU  - Bernsmeier,C
AU  - Napoli,S
AU  - Bernal,W
AU  - Wendon,J
AU  - Miquel,R
AU  - Menon,K
AU  - Patel,VC
AU  - Smith,J
AU  - Atkinson,SR
AU  - Triantafyllou,E
AU  - McPhail,MJ
DO  - 10.1016/j.jhep.2022.10.031
EP  - 573
PY  - 2023///
SN  - 0168-8278
SP  - 558
TI  - Lysophosphatidylcholines modulate immunoregulatory checkpoints in peripheral monocytes and are associated with mortality in people with acute liver failure.
T2  - Journal of Hepatology
UR  - http://dx.doi.org/10.1016/j.jhep.2022.10.031
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36370949
UR  - https://www.sciencedirect.com/science/article/pii/S0168827822032883?via%3Dihub
UR  - http://hdl.handle.net/10044/1/100880
VL  - 78
ER  -
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