Leader(s)
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Lotersztajn Sophie
- 01 57 27 74 29
- sophie.lotersztajn@inserm.fr
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Gilgenkrantz Hélène
- 01 57 27 75 30
- helene.gilgenkrantz@inserm.fr
Inflammatory and stress responses in chronic liver diseases (INVolVED)
Team Lotersztajn / Gilgenkrantz
Department Hepato-Gastroenterology Department
Line-up
Clinicians
Presentation
Our team studies the mechanisms underlying chronic liver disease progression to cirrhosis and its complications, with an emphasis on the identification of prognosis markers and therapeutic targets for steatotic liver diseases (SLD). Our research program focuses on the identification of immunometabolic targets and biomarkers of liver and systemic inflammation.
Metabolic associated fatty liver disease (MAFLD) and alcoholic related liver disease (ArLD) are leading causes of liver diseases worldwide. They share common pathogenic features including steatosis and steatohepatitis that lead to fibrosis and cirrhosis. Persistent inflammation is a driving force of liver fibrosis progression during MAFLD and ArLD. Among patients with cirrhosis, excessive inflammation results in the development of multiorgan failure (defining acute-on-chronic liver failure or ACLF), which often leads to death. The lack of treatment highlights the urgent need for new prognosis markers and specific therapeutic targets that could limit liver injury, fibrosis, progression of cirrhosis to ACLF, and favour liver regeneration.
Non canonical autophagy in monocytes from patients with cirrhosis
Our studies include:
- The mechanisms underlying monocyte/macrophage reprogramming and the impact on fatty liver disease progression to fibrosis, and on liver regeneration. We target specific pathways we recently uncovered including canonical and non canonical autophagy, and lipid metabolic reprogramming (Gual 2017 Am J Physiol; Weiss J Hepatol 2017; Habib Gut 2018; Tardelli Hepatology 2019; Tardelli J Lipid Res 2019; Allaire J Hepatol 2019; Wan Science Translational Medicine 2020; , Gilgenkrantz J Hep 2021 ; Autophagy 2020 ; Gilgenkrantz Hepatology 2023; Allaire J Hep Rep 2023).
- The role of adaptive immune cells (Th17) and non conventional T lymphocytes, in particular Mucosal associated invariant T (MAIT) cells, in the control of inflammation at sequential steps of SLD progression and regression (Hegde Nat Com 2018; Toubal Nat Rev Immunol 2019; Mabire Nat Com 2023).
- Novel biomarkers and clinical studies evaluating new therapeutic strategies in MAFLD, cirrhosis, transplantation and acute on chronic liver failure (ACLF), a syndrome we characterized and in which systemic inflammation is a major trigger (Weiss J Hepatol 2017; Claria Hepatology 2018; Fernandez Gastroenterology 2019; Zaccherini J Hep Rep 2020; Arroyo New Engl J Medicine 2020; Karvellas Transplantation 2021; Durand Liver International 2021; Zaccherinin J Hep 2021; Weiss Front Immunol 2021; Weiss Gut 2023).
- The SIRIC Project InsiTu (Insights into cancer: from inflammation to Tumour), led by Pr Valerie Paradis, in which we characterize the factors that cause and sustain chronic inflammation and identify the key mechanisms through which inflammation triggers the transition from chronic inflammatory disease to liver cancer.
Networks In addition to SIRIC InsiTu, our group is a founding team of the European Consortium for the study of Chronic Liver Failure (EF-CLIF) and the French-Indian network (LIA) and Labec Inflamex.
Funding: Inserm, Université Paris-Diderot, Laboratory of Excellence Inflamex, National research agency (ANR), Fondation pour la Recherche médicale (FRM), french associations for the study of the liver and for digestive diseases (AFEF, SNFGE), SIRIC, Inserm-Transfert, Assistance Publique Hôpitaux de Paris (PHRC), H2020.
Precision Cut Liver Slices (PCLS) of human liver with cirrhosis treated with Ac-6FP: Reduction in MAIT cell activation (V⍺7.2/CD69)
Landmark publications
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Publication date : 01 August 2023 More
Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)
Gut.
Authors : Weiss Emmanuel Carlos de la Peña-Ramirez Ferran Aguilar Juan-Jose Lozano Cristina Sánchez-Garrido Patricia Sierra Pedro Izquierdo-Bueno Martin Juan Manuel Diaz François Fenaille Florence A Castelli Gustot Thierry Wim Laleman Agustín Albillos Carlo Alessandria Marco Domenicali Paolo Caraceni Salvatore Piano Faouzi Saliba Stefan Zeuzem Alexander L Gerbes Julia A Wendon Christian Jansen Wenyi Gu Maria Papp Raj Mookerjee Carmine Gabriele Gambino Cesar Jiménez Ilaria Giovo Giacomo Zaccherini Manuela Merli Antonella Putignano Frank Erhard Uschner Thomas Berg Tony Bruns Christian Trautwein Alexander Zipprich Rafael Bañares José Presa Joan Genesca Victor Vargas Javier Fernández Mauro Bernardi Paolo Angeli Rajiv Jalan Joan Claria Christophe Junot Moreau Richard Jonel Trebicka Vicente Arroyo
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Publication date : 23 May 2023 More
Cell metabolism-based therapy for liver fibrosis, repair and hepatocellular carcinoma
Hepatology.
Authors : Gilgenkrantz Hélène Paradis Valérie Lotersztajn Sophie
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Publication date : 16 May 2023 More
Monoacylglycerol lipase reprograms hepatocytes and macrophages to promote liver regeneration
JHEP Rep.
Authors : Allaire Manon Al Sayegh Rola Mabire Morgane Hammoutene Adel Matthieu Siebert Caër Charles Cadoux Mathilde Wan Jinghong Habib Aida Le Gall Maude Pierre de la Grange Hervé Guillou Catherine Postic Paradis Valérie Lotersztajn Sophie Gilgenkrantz Hélène
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Publication date : 01 April 2023 More
MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming
Nature Commun.
Authors : Mabire Morgane Pushpa Hegde Hammoutene Adel Wan Jinghong Caër Charles Al Sayegh Rola Cadoux Mathilde Weiss Emmanuel Tristan Thibault-Sogorb Olivier Lantz Michèle Goodhardt Paradis Valérie Pierre de la Grange Gilgenkrantz Hélène Lotersztajn Sophie
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Publication date : 01 June 2021 More
Targeting cell-intrinsic metabolism for antifibrotic therapy
J Hepatol.
Authors : Gilgenkrantz Hélène Mallat Ariane Moreau Richard Lotersztajn Sophie
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Publication date : 05 February 2021 More
Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF
Front Immunol.
Authors : Weiss Emmanuel Pierre de la Grange Mylène Defaye Juan José Lozano Ferrán Aguilar Pushpa Hegde Ariane Jolly Moga Lucile Sukriti Sukriti Banwari Agarwal Haqeeqat Gurm Tanguy Marion Poisson Johanne Joan Clària Paer-Selim Abback Perianin Axel Gautam Mehta Rajiv Jalan Francoz Claire Rautou Pierre-Emmanuel Lotersztajn Sophie Vicente Arroyo Durand François Moreau Richard
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Publication date : 28 May 2020 More
Acute-on-Chronic Liver Failure
N Engl J Med.
Authors : Vicente Arroyo Moreau Richard Rajiv Jalan
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Publication date : 15 April 2020 More
LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling.
Sci Transl Med
Authors : Wan Jinghong Weiss Emmanuel Ben Mkaddem Sanae Mabire Morgane Pierre-Marie Choinier Olivia Picq Tristan Thibault-Sogorb Pushpa Hegde Dorsa Pishvaie Bens Marcelle Linda Broer Gilgenkrantz Hélène Moreau Richard Saveanu Loredana Patrice Codogno Monteiro Renato Lotersztajn Sophie
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Publication date : 01 October 2019 More
Mucosal-associated invariant T cells and disease
Nat Rev Immunol.
Authors : Toubal A Nel I Lotersztajn Sophie Lehuen A
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Publication date : 01 May 2019 More
Autophagy in liver diseases: Time for translation?
J Hepatol.
Authors : Allaire Manon Rautou Pierre-Emmanuel Codogno P Lotersztajn Sophie
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Publication date : 09 October 2018 More
Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver
Gut. 2018
Authors : Habib Aida Chokr D Wan Jinghong Hegde P Mabire Morgane Siebert M Ribeiro-Parenti Lara Le Gall Maude Letteron Philippe Pilard N Mansouri Abdellah Brouillet A Tardelli M Weiss Emmanuel Le Faouder P Guillou H Cravatt BF Moreau Richard Trauner M Lotersztajn Sophie
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Publication date : 01 June 2018 More
AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation.
J Hepatol.
Authors : Abitbol S Dahmani R Coulouarn C Ragazzon B Mlecnik B Senni N Savall M Bossard P Sohier P Drouet V Tournier E Dumont F Sanson R Calderaro J Zucman-Rossi J Vasseur-Cognet M Just PA Terris B Perret C Gilgenkrantz Hélène
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Publication date : 01 June 2018 More
Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver
Nat Commun.
Authors : Hegde P Weiss Emmanuel Paradis Valérie Wan Jinghong Mabire Morgane Sukriti S Rautou Pierre-Emmanuel ALBUQUERQUE Miguel Picq O Gupta AC Ferrere G Gilgenkrantz Hélène Kiaf B Toubal A Beaudoin L Letteron Philippe Moreau Richard Lehuen A Lotersztajn Sophie