Weiss / Gilgenkrantz

Our team is studying the mechanisms that control the progression of chronic liver disease to cirrhosis and its complications, with the aim of identifying prognostic markers and therapeutic targets for hepatic steatosis. Our aim is to identify immunometabolic targets and biomarkers of systemic and hepatic inflammation.

Metabolic liver disease (MAFLD) and alcoholic liver disease (ArLD) are the two leading causes of chronic liver disease worldwide. They share a common pathophysiology including steatosis, steatohepatitis leading to fibrosis and cirrhosis. Inflammation is a key factor in the progression of both MAFLD and ArLD. It also plays a major role in its regression. In cirrhosis, exacerbated inflammation leads to multi-organ failure, defining the ACLF (acute-on-chronic liver failure) syndrome, which has a particularly poor prognosis. In the absence of treatment, there is an urgent need to develop prognostic markers and discover new therapeutic targets to limit liver damage and disease progression to cirrhosis or ACLF, and promote liver regeneration.

Non-canonical autophagy in blood monocytes from patients with cirrhosis

Our work focuses on

1. The mechanisms that enable intrinsic or extrinsic reprogramming of monocytes/macrophages and its consequences on chronic liver disease progression and regeneration. In particular, we target pathways we have recently identified such as autophagy (canonical and non-canonical) and lipid metabolism(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).
2. The role of adaptive immunity cells (Th17) and unconventional T cells, notably MAIT (Mucosal associated invariant T cells), in controlling inflammation during MAFLD progression and regression(Hegde Nat Com 2018; Toubal Nat Rev Immunol 2019; Mabire Nat Com 2023).
3. The identification of new biomarkers and therapeutic strategies in MAFLD, cirrhosis, liver transplantation and ACLF(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).
4. the factors that cause and maintain chronic inflammation during the liver fibrosis/cancer transition as part of the SIRIC InsiTu project (Insights into cancer: from inflammation to Tumour, Pr V Paradis).

National networks: Ourteam is a member of the Inflamex labex and belongs to several

internationalnetworks , the European consortium EF-CLIF (European Consortium for the study of Chronic Liver Failure, founding member) and a Franco-Indian network as part of an LIA.

Funding: Inserm, Université Paris-Cité, Labex Inflamex, ANR, Fondation pour la Recherche médicale, Associations française pour l’Etude du foie (AFEF) et Gastroentérologie (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: reduced activation of MAIT(V⍺7.2/CD69) cells.