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Riva A, Palma E, Devshi D, et al. Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity. Front Physiol. 2021;12:632502doi: 10.3389/fphys.2021.632502.
Riva, A., Palma, E., Devshi, D., Corrigall, D., Adams, H., Heaton, N., Menon, K., Preziosi, M., Zamalloa, A., Miquel, R., Ryan, J. M., Wright, G., Fairclough, S., Evans, A., Shawcross, D., Schierwagen, R., Klein, S., Uschner, F. E., Praktiknjo, M., Katzarov, K., Hadzhiolova, T., Pavlova, S., Simonova, M., Trebicka, J., Williams, R., & Chokshi, S. (2021). Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity. Frontiers in physiology, 12632502. https://doi.org/10.3389/fphys.2021.632502
Riva, Antonio, et al. "Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity." Frontiers in physiology vol. 12 (2021): 632502. doi: https://doi.org/10.3389/fphys.2021.632502
Riva A, Palma E, Devshi D, Corrigall D, Adams H, Heaton N, Menon K, Preziosi M, Zamalloa A, Miquel R, Ryan JM, Wright G, Fairclough S, Evans A, Shawcross D, Schierwagen R, Klein S, Uschner FE, Praktiknjo M, Katzarov K, Hadzhiolova T, Pavlova S, Simonova M, Trebicka J, Williams R, Chokshi S. Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity. Front Physiol. 2021 Mar 10;12:632502. doi: 10.3389/fphys.2021.632502. eCollection 2021. PMID: 33776793; PMCID: PMC7987668.
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Front Physiol. 2021 Mar 10;12:632502. doi: 10.3389/fphys.2021.632502. eCollection 2021.

Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity.

Frontiers in physiology

Antonio Riva, Elena Palma, Dhruti Devshi, Douglas Corrigall, Huyen Adams, Nigel Heaton, Krishna Menon, Melissa Preziosi, Ane Zamalloa, Rosa Miquel, Jennifer M Ryan, Gavin Wright, Sarah Fairclough, Alexander Evans, Debbie Shawcross, Robert Schierwagen, Sabine Klein, Frank E Uschner, Michael Praktiknjo, Krum Katzarov, Tanya Hadzhiolova, Slava Pavlova, Marieta Simonova, Jonel Trebicka, Roger Williams, Shilpa Chokshi

Affiliations

  1. Institute of Hepatology, Foundation for Liver Research, London, United Kingdom.
  2. Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
  3. Department of Gastroenterology, Basildon University Hospital, Basildon, United Kingdom.
  4. Department of Gastroenterology, Royal Berkshire Hospital, Reading, United Kingdom.
  5. Institute of Liver Studies, King's College London, London, United Kingdom.
  6. Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
  7. Gastrointestinal and Liver Services, Royal Free Hospital, London, United Kingdom.
  8. Translational Hepatology, Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt, Germany.
  9. Department of Internal Medicine I, University of Bonn, Bonn, Germany.
  10. Department of Gastroenterology, Hepatobiliary Surgery and Transplantology, Military Medical Academy, Sofia, Bulgaria.
  11. European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain.

PMID: 33776793 PMCID: PMC7987668 DOI: 10.3389/fphys.2021.632502

Abstract

BACKGROUND AND AIMS: Immunoregulatory checkpoint receptors (CR) contribute to the profound immunoparesis observed in alcohol-related liver disease (ALD) and

METHODS: In Alcoholic Hepatitis (AH;

RESULTS: Soluble-TIM3 was the dominant plasma soluble-CR in ALD vs. HC (

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.

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.

Keywords: TIM3; alcohol; alcohol-related liver disease; biomarker; immune checkpoint

Conflict of interest statement

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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