Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity.
TIM3
alcohol
alcohol-related liver disease
biomarker
immune checkpoint
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
11
2020
accepted:
10
02
2021
entrez:
29
3
2021
pubmed:
30
3
2021
medline:
30
3
2021
Statut:
epublish
Résumé
Immunoregulatory checkpoint receptors (CR) contribute to the profound immunoparesis observed in alcohol-related liver disease (ALD) and In Alcoholic Hepatitis (AH; Soluble-TIM3 was the dominant plasma soluble-CR in ALD vs. HC ( Alcohol-related liver disease patients exhibit supra-physiological plasma levels of soluble-TIM3, particularly those with greater disease severity. This is also associated with increased levels of soluble TIM3-ligands and membrane-TIM3 expression on immune cells. Soluble-TIM3 can block the TIM3-ligand synapse and improve anti-bacterial immunity; however, the increased levels of soluble TIM3-binding ligands in patients with ALD negate any potential immunostimulatory effects. We believe that anti-TIM3 neutralizing antibodies currently in Phase I clinical trials or soluble-TIM3 should be investigated further for their ability to enhance anti-bacterial immunity. These agents could potentially represent an innovative immune-based supportive approach to rescue anti-bacterial defenses in ALD patients.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Immunoregulatory checkpoint receptors (CR) contribute to the profound immunoparesis observed in alcohol-related liver disease (ALD) and
METHODS
METHODS
In Alcoholic Hepatitis (AH;
RESULTS
RESULTS
Soluble-TIM3 was the dominant plasma soluble-CR in ALD vs. HC (
CONCLUSIONS
CONCLUSIONS
Alcohol-related liver disease patients exhibit supra-physiological plasma levels of soluble-TIM3, particularly those with greater disease severity. This is also associated with increased levels of soluble TIM3-ligands and membrane-TIM3 expression on immune cells. Soluble-TIM3 can block the TIM3-ligand synapse and improve anti-bacterial immunity; however, the increased levels of soluble TIM3-binding ligands in patients with ALD negate any potential immunostimulatory effects. We believe that anti-TIM3 neutralizing antibodies currently in Phase I clinical trials or soluble-TIM3 should be investigated further for their ability to enhance anti-bacterial immunity. These agents could potentially represent an innovative immune-based supportive approach to rescue anti-bacterial defenses in ALD patients.
Identifiants
pubmed: 33776793
doi: 10.3389/fphys.2021.632502
pmc: PMC7987668
doi:
Types de publication
Journal Article
Langues
eng
Pagination
632502Informations de copyright
Copyright © 2021 Riva, Palma, Devshi, Corrigall, Adams, Heaton, Menon, Preziosi, Zamalloa, Miquel, Ryan, Wright, Fairclough, Evans, Shawcross, Schierwagen, Klein, Uschner, Praktiknjo, Katzarov, Hadzhiolova, Pavlova, Simonova, Trebicka, Williams and Chokshi.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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