General Pathology 2

The research activities of the Laboratory of General Pathology focus mainly on the understanding of molecular and cellular mechanisms, with particular reference to the induction of immune responses, at the root of the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The global prevalence of NAFLD is estimated at around 25% and continues to increase due to the increasing prevalence of obesity. NAFLD is the most common cause of chronic liver disease and its advanced form, known as non-alcoholic steatohepatitis (NASH), has rapidly become a leading cause of cirrhosis and liver transplantation globally. Despite intense research, to date, there are still no approved therapies for the treatment of NASH. Based on previous studies that have shown an association between adaptive immune responses triggered by oxidative stress-derived antigens (OSA) and the severity of NASH, the ongoing research activity aims to: a) define the relative contribution B / T lymphocytes in supporting the inflammatory responses associated with NASH; b) to characterize the immune mechanisms involved in the progression of NASH towards cirrhosis and hepatocellular carcinoma (HCC); c) explore the possible therapeutic effects of interference with immune responses in the context of experimental NASH.

1. Gadipudi LL, Ramavath NN, Provera A, Reutelingsperger C, Albano E, Perretti M, Sutti S. Annexin A1 treatment prevents the evolution to fibrosis of experimental nonalcoholic steatohepatitis. Clin Sci (Lond). 2022 May 13;136(9):643-656. doi: 10.1042/CS20211122.
2. Foglia B, Sutti S, Cannito S, Rosso C, Maggiora M, Autelli R, Novo E, Bocca C, Villano G, Ramavath NN, Younes R, Tusa I, Rovida E, Pontisso P, Bugianesi E, Albano E, Parola M. Hepatocyte-Specific Deletion of HIF2α Prevents NASH-Related Liver Carcinogenesis by Decreasing Cancer Cell Proliferation. Cell Mol Gastroenterol Hepatol. 2022;13(2):459-482. doi: 10.1016/j.jcmgh.2021.10.002.
3. Mattu S, Zavattari P, Kowalik MA, Serra M, Sulas P, Pal R, Puliga E, Sutti S, Foglia B, Parola M, Albano E, Giordano S, Perra A, Columbano A. Nrf2 Mutation/Activation Is Dispensable for the Development of Chemically Induced Mouse HCC. Cell Mol Gastroenterol Hepatol. 2022;13(1):113-127. doi:10.1016/j.jcmgh.2021.08.011.
4. Ramavath NN, Gadipudi LL, Provera A, Gigliotti LC, Boggio E, Bozzola C, Albano E, Dianzani U, Sutti S. Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair. Front Immunol. 2021 Dec 3;12:786680. doi: 10.3389/fimmu.2021.786680.
5. Sutti S, Albano E. Adaptive immunity: an emerging player in the progression of NAFLD. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):81-92. doi: 10.1038/s41575-019-0210-2.
6. Foglia B, Sutti S, Pedicini D, Cannito S, Bocca C, Maggiora M, Bevacqua MR, Rosso C, Bugianesi E, Albano E, Novo E, Parola M. Oncostatin M, A Profibrogenic Mediator Overexpressed in Non-Alcoholic Fatty Liver Disease, Stimulates Migration of Hepatic Myofibroblasts. Cells. 2019 Dec 20;9(1):28. doi: 10.3390/cells9010028.
7. Sutti S, Bruzzì S, Heymann F, Liepelt A, Krenkel O, Toscani A, Ramavath NN, Cotella D, Albano E, Tacke F. CX3CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation. Cells. 2019 Sep 18;8(9):1099. doi: 10.3390/cells8091099.
8. Bruzzì S, Sutti S, Giudici G, Burlone ME, Ramavath NN, Toscani A, Bozzola C, Schneider P, Morello E, Parola M, Pirisi M, Albano E. B2-Lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease (NAFLD). Free Radic Biol Med. 2018 Aug 20;124:249-259. doi: 10.1016/j.freeradbiomed.2018.06.015.
9. Morello E, Sutti S, Foglia B, Novo E, Cannito S, Bocca C, Rajsky M, Bruzzì S, Abate ML, Rosso C, Bozzola C, David E, Bugianesi E, Albano E, Parola M. Hypoxia-inducible factor 2α drives nonalcoholic fatty liver progression by triggering hepatocyte release of histidine-rich glycoprotein. Hepatology. 2018 Jun;67(6):2196-2214. doi: 10.1002/hep.29754.
10. Sutti S, Heymann F, Bruzzì S, Peusquens J, Trautwein C, Albano E, Tacke F. CX3CR1 modulates the anti-inflammatory activity of hepatic dendritic cells in response to acute liver injury. Clin Sci (Lond). 2017 Sep;131(17):2289-2301. doi: 10.1042/CS20171025.

1.  Prof. Umberto Dianzani (University of East Piedmont) to study the role of ICOS/ICOS-L in a) modulating macrophage functional capacities during the evolution of acute liver injury; b) modulating immune responses associated with NASH evolution toward fibrosis.
2. Prof. Maurizio Parola (University of Turin) to study the role of hypoxia-related molecular mediators in the development of NASH-associated cancerogenesis.
3. Prof. Flavia Prodam (University of East Piedmont) to study the possible therapeutic effects of ketogenic diet administration during NASH.
4. Prof. Dianzani Irma (University of East Piedmont) to study the interplay between gut microbiota and obesity in the onset of colon cancer.
5. Prof. Frank Tacke (Charité University Medical Center, Berlin, Germany) to study the interplay between T-lymphocytes and macrophages in the evolution of acute and chronic liver injury.

1. Advanced project on AGING (2019): WORK-PACKAGE TITLE: Study of the mechanisms causing sarcopenia associated with non-alcoholism fatty liver disease (NAFLD) (work-package coordinator).
2. Projects FAR 2019: “Role of co-stimulatory molecules in the regulation of liver damage healing processes and in the development of fibrosis". (Role: PI)

Salvatore Sutti – Professore Associato di Patologia Generale - PI

Alessia Provera – PhD student in Medical Biotechnology and Sciences

Federica Fornì – Master’s degree student in Medical Biotechnologies

Antonio Tommaso Pinto – Master’s degree student in Medical Biotechnologies