2019-01-16 13.42.37

Inflammatory and stress responses in chronic liver diseases

Team Lotersztajn / Gilgenkrantz

Department Hepato-Gastroenterology Department

 

Team leader

 

Line-up

 

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 fatty liver diseases.Our research program focuses on the identification of immunometabolic targets and biomarkers of liver and systemic inflammation.

Non-alcoholic and alcoholic fatty liver diseases (NAFLD, ALD) are leading causes of liver diseases worldwide. They share common pathogenic features including steatosis and steatohepatitis (alcoholic-ASH and non-alcoholic-NASH) that lead to fibrosis and cirrhosis. Persistent inflammation is a driving force of liver fibrosis progression during NAFLD and ALD. Among patients with cirrhosis, excessive inflammation results in the development of multiorgan failure (defining acute-on-chronic liver failure, 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.

Ongoing studies include:

  1. 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, macrophage apoptosis and lipid metabolic targets such as monoacylglycerol lipase (Louvet, Hepatology 2011 ; Mallat, J Hepatol 2013 ; Mallat Am J Physiol 2013 ; Wan Hepatology 2014 ; Gandoura J Hepatol 2015 ; Lodder Autophagy 2015 ; Denaes, 2016, Sci Rep ; Gual, 2017 Am J Physiol ;  Weiss, J Hepatol 2017 ; Habib Gut 2018 ;  Tardelli, Hepatology 2019 ; Tardelli, J Lipid Res 2019 ; Allaire, J Hepatol 2019).
  2. 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 fatty liver progression (Guillot, Hepatology 2014 ; Hegde Nat Com 2018 ; Toubal Nat Rev Immunol 2019).
  3. Novel biomarkers, targets and clinical studies evaluating new therapeutic strategies in NAFLD, cirrhosis and ACLF, a syndrome we characterized and in which systemic inflammation is a major trigger (Moreau, Gastroenterology 2013,Gustot Hepatology 2016, Claria J Hepatol 2016, Claria Hepatology 2018, Fernandez, Gastroenterology 2019).
  4. The RHU QUID-NASH projecs, led by Pr Dominique Valla, aims to develop a virtual biopsy for diabetic patients with non-alcoholic fatty liver disease, and to improve the development of new treatments. The project will combine radiomic, métabolomic, transcriptomic and genomic data.

Networks : In addition to RHU QUID-NASH, 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 Labex 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), RHU QUID-NASH Inserm-Transfert, Assistance Publique Hopitaux de Paris (PHRC),

 

Landmark publications

  • Publication date : 01 July 2020 More

    Glutamate Signaling in Alcohol-associated Fatty Liver: “Pas de Deux” Hepatology

    Autors : Ariane Mallat Lotersztajn Sophie

  • Publication date : 15 April 2020 More

    LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling. Sci Transl Med

    Autors : 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

  • Publication date : 01 October 2019 More

    Mucosal-associated invariant T cells and disease Nat Rev Immunol. 2019 Oct;19(10):643-657.

    Autors : Toubal A Nel I Lotersztajn Sophie Lehuen A

  • Publication date : 01 May 2019 More

    Autophagy in liver diseases: Time for translation? J Hepatol. 2019 May;70(5):985-998.

    Autors : Allaire Manon Rautou Pierre-Emmanuel Codogno P Lotersztajn Sophie

  • Publication date : 01 April 2019 More

    Age and liver transplantation J Hepatol. 2019 Apr;70(4):745-758.

    Autors : Durand François Levitsky J Cauchy F Gilgenkrantz Hélène Soubrane Olivier Francoz Claire

  • Publication date : 01 December 2018 More

    Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis Gastroenterology. 2018 Dec;155(6):1816-1827.May;66(5):930-941

    Autors : Moreau Richard Elkrief Laure Bureau C Perarnau JM Thévenot T Saliba F Louvet A Nahon P Lannes A Anty R Hillaire S Pasquet B Ozenne V Rudler M Ollivier-Hourmand I Robic MA Di Martino V Ripault MP Pauwels A Grangé JD Carbonell N Bronowicki JP Payancé A Rautou Pierre-Emmanuel Valla Dominique Gault N Lebrec D NORFLOCIR Trial Investigators

  • Publication date : 09 October 2018 More

    Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver Gut. 2018 Oct 9. pii: gutjnl-2018-316137. doi: 10.1136/gutjnl-2018-316137

    Autors : 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

  • 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. 2018 Jun;68(6):1203-1213

    Autors : 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

  • Publication date : 01 June 2018 More

    Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver Nat Commun. 2018 Jun 1;9(1):2146

    Autors : 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

  • Publication date : 14 August 2015 More

    Macrophage autophagy protects against liver fibrosis in mice. Autophagy. 2015;11(8):1280-92.

    Autors : Lodder J Denaës T Chobert MN Wan Jinghong El Benna Jamel Pawlotsky JM Lotersztajn Sophie Teixeira-Clerc F

  • Publication date : 06 January 2014 More

    M2 Kupffer cells promote M1 Kupffer cell apoptosis: a protective mechanism against alcoholic and nonalcoholic fatty liver disease Hepatology. 2014 Jan;59(1):130-42

    Autors : Wan Jinghong Benkdane M Teixeira-Clerc F Bonnafous S Louvet A Lafdil F Pecker F Tran A Gual A Mallat A Lotersztajn Sophie Pavoine C

 
 

Latest Publications

  • Publication date : 03 August 2020 More

    The protein kinase A negatively regulates reactive oxygen species production by phosphorylating gp91phox/NOX2 in human neutrophils Free Radic Biol Med

    Autors : Houssam Raad Hussein Mouawia Hamad Hassan Mohamed El-Seblani Riad Arabi-Derkawi Tarek Boussetta Gougerot-Pocidalo Marie-Anne Dang Pham My-Chan El Benna Jamel

  • Publication date : 11 July 2020 More

    Ferroptosis in Liver Diseases: An Overview Int J Mol Sci

    Autors : Martina Maria Capelletti Manceau Hana Puy Hervé Katell Peoc'h

  • Publication date : 19 June 2020 More

    Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine J Crohns Colitis

    Autors : Al Nabhani Z Berrebi D Martinez-Vinson C Montcuquet N Madre C Roy Maryline Ogier-Denis Eric Dussaillant M Cerf-Bensussan N Zouali H Daniel F Barreau F Hugot Jean-Pierre