Immunology, Transplantation and Infectious diseases

Immunopathology

Group leader

Luca Guidotti

Research programs of Immunopathology Unit aim to dissect the cellular and molecular mechanisms responsible for immunopathological responses of the liver, with emphasis on the responses that occur during infection with hepatitis B virus (HBV). HBV is a noncytopathic virus that cause acute and chronic hepatitis of variable duration and severity. Over 250 million people worldwide are chronically infected by HBV and almost a million of them die each year from complications (e.g. cirrhosis and hepatocellular carcinoma, HCC) of this infection.

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Research activity

Taking advantage of infected patients, proprietary animal models of infection and new technological advances in the field of static and dynamic imaging, Immunopathology Unit tackles unresolved issues that include the means by which innate and adaptive immune cells traffic and function within the normal, cirrhotic or cancerous livers. This information is and will be used to devise novel immunotherapeutic strategies to cure chronic HBV infection and prevent its life-threatening sequelae.

Selected publications

Iannacone M. and L.G. Guidotti✉. Rethinking HBV therapies. Nature Outlook series, Nature In press. Impact Factor: 49.962.

Aiolfi R., G. Sitia, M. Iannacone, I. Brunetta, L.G. Guidotti†✉, Z.M Ruggeri†✉ (†Co-Last Authors) Arenaviral infection causes bleeding in mice due to reduced serotonin release from platelets. Science Signaling. 2022 15, 722 DOI: 10.1126/scisignal.abb0384. Impact Factor: 8.192

Fumagalli V., V. Venzin, P. Di Lucia, F. Moalli, X. Ficht, G. Ambrosi, L. Giustini, F. Andreata, M. Grillo, D. Magini, M. Ravà, C. Friedrich, J.D. Fontenot, P. Bousso, S.A., S. Khan, M. Baca, E. Vivier,G. Gasteiger, M. Kuka M. Kuka, L.G. Guidotti†✉, Matteo Iannacone†✉ (†Co-Last Authors). Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability. Science Immunology. In Press. Impact Factor: 13.44

Iannacone M✉ and L.G. Guidotti✉. Immunobiology and pathogenesis of hepatitis B virus infection. Nature Reviews Immunology, 2022 22:19-32. doi: 10.1038/s41577-021-00549-4. PMID: 34002067. Impact Factor: 53.106

Di Fabio, R., L. Bencheva, R. De Francesco, L. Donnici, V.Summa, E. Monteagudo, M.Iannacone, L.G. Guidotti✉. Preclinical assessment of capsid assembly modulators (CAMs) of varying potency revealed a novel class of picomolar-acting CAMs inducing neither significant HBcAg cytoplasmic retention nor adverse interactions with HBcAg-specific adaptive immunity. J. Hepatol. 73:S5, 2020. Impact Factor: 25.083.

Fumagalli V., M. Ravà, D. Marotta, P. Di Lucia, C. Laura, E. Sala, M. Grillo, E. Bono, L. Giustini, C. Perucchini, M. Mainetti, A. Sessa, J.M Garcia-Manteiga, L. Donnici, L. Manganaro, S. Delbue, V. Broccoli, R. De Francesco, P. D’Adamo, M. Kuka, L.G. Guidotti†✉, Matteo Iannacone†✉ (†Co-Last Authors). Administration of aerosolized SARS-CoV-2 to K18-hACE2 mice uncouples respiratory infection from fatal neuroinvasion. Science Immunology 2022 28;7:eabl9929. doi: 10.1126/sciimmunol.abl9929. PMID: 34812647. Impact Factor: 13.44

De Simone G, F. Andreata, C. Bleriot, V. Fumagalli, C. Laura, J. M. Garcia-Manteiga, P. Di Lucia, S. Gilotto, X. Ficht, F.F. De Ponti, E.B. Bono, L. Giustini, G. Ambrosi, M. Mainetti, P. Zordan, A. P. Bénéchet, M. Ravà, S. Chakarov, F. Moalli, M. Bajenoff, Luca G. Guidotti†, Florent Ginhoux†✉ and Matteo Iannacone†✉ (†Co-Last Authors). Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. Immunity 2021 14;54:2089-2100.e8. doi: 10.1016/j.immuni.2021.05.005. PMID: 34469774. COVER PAGE. Impact Factor: 31.745

Fumagalli V., P. Di Lucia, V. Venzin, E. Bono, R. Jordan, C. Frey, W. Delaney, F.V. Chisari, L.G. Guidotti†✉, M. Iannacone†✉ (†Co-Last Authors). Serum HBsAg clearance has minimal impact on CD8+ T cell responses in mouse models of HBV infection. J. Exp. Med. 2020 2;217:e20200298. doi: 10.1084/jem.20200298. PMID: 32761167. Impact Factor: 14.307

Bénéchet A.P., G. De Simone, P. Di Lucia, F. Cilenti, F. Moalli, N. Le Bert, G. Barbiera, E. Lusito, V. Fumagalli, V. Bianchessi, P. Zordan, E. Bono, L. Giustini, W.V. Bonilla, C. Bleriot, G. Gonzalez-Aseguinolaza, D.D. Pinschewer, L. Naldini, M. Kuka, F. Ginhoux, A. Cantore, A. Bertoletti, R. Ostuni, L.G. Guidotti†✉, M. Iannacone†✉ (†Co-Last Authors). Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming. Nature 2019 574:200-205. doi: 10.1038/s41586-019-1620-6. Epub 2019 Oct 2. PMID: 31582858. Impact Factor: 49.962.

Fioravanti J, P. Di Lucia, D. Magini, F. Moalli, C. Boni, A.P. Benechet, V. Fumagalli, D. Inverso, A. Vecchi, A. Fiocchi, S. Wieland, R. Purcell, C. Ferrari C, F.V. Chisari, L.G. Guidotti†✉ and M. Iannacone†✉(†Co-Last Authors). Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology. J Hepatol. 2017 67:543-548. doi: 10.1016/j.jhep.2017.04.020. PMID: 28483675. Impact Factor: 25.083

Guidotti LG ✉, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez- Aseguinolaza G, Protzer U, Chisari FV, Ruggeri ZM, Isogawa M, Sitia G, Iannacone M ✉. Immunosurveillance of the liver by intravascular effector CD8+ T cells. Cell 2015 Apr 23;161(3):486-500. Impact Factor: 41.582

Sitia G, Aiolfi R, Di Lucia P, Mainetti M, Fiocchi A, Mingozzi F, Esposito A, Ruggeri ZM, Chisari FV, Iannacone M and Guidotti LG ✉. Anti-platelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B. PNAS Plus, USA. 2012 Aug 7;109(32):E2165-72. Impact Factor: 11.205.

Sitia G, Iannacone M, Aiolfi R, Isogawa M, van Rooijen N, Scozzesi C, Bianchi ME, von Andrian UH, Chisari FV, Guidotti LG✉. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis. Plos Pathogens. 2011; 7(6):e1002061.

Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, Chisari FV, Ruggeri ZM, Guidotti LG ✉ . Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat Med. 2005 Nov;11(11):1167-9.

Sitia G, Isogawa M, Iannacone M, Campbell IL, Chisari FV, Guidotti LG ✉ . MMPs are required for recruitment of antigen non-specific mononuclear cells into the liver by CTLs. J Clinical Investigation. 2004 Apr 15; 113(8): 1158–1167.