Immunology, Transplantation and Infectious diseases
Autoimmunity and vascular inflammation
Inflammation is a homeostatic process triggered by microbial components and tissue damage. The cellular components that reach the extracellular environment as a consequence of cellular stress and death or activation are recognized by leukocytes which in turn determine the eventual outcome of the process in terms of tissue regeneration and repair or on the other handof inflammatory damage that becomes chronic and self- suffcient, causing tissue remodeling and loss of function. Process abnormalities, particularly in the phagocytic clearance of dead cells, debris, activated platelets, microparticles play a key role in autoimmune diseases.
These alterations contribute to the origin of autoimmunity and to the amplification and acceleration of the clinical features that determine the specific characteristics of each disease. Persistent vascular inflammation, in particular, reflects a vicious circle through which in ammatory leukocytes are attracted and activated in the walls of vessels that further damage. Restoring the regulatory network of signals connecting leukocytes, platelets and endothelial cells could be useful to limit the harmful consequences of the process.
Research activity
The group is particularly interested in the identification of molecular mechanisms that lead to the perpetuation of the inflammatory response and autoimmunity, with particular attention to the role of endogenous adjuvants released after necrosis (Pattern Molecular Damage-Associated, DAMPS, or Alarmins) and humoral innate immunity.
De Lorenzo R, Sciorati C, Lorè NI, Capobianco A, Tresoldi C; Cirillo DM, Ciceri F, Corti A, Rovere-Querini P, Manfredi AA. Chitinase-3-like protein-1 at hospital admission predicts COVID-19 outcome: a prospective cohort study. Scientific Reports, 2022 in press. doi.org/10.1038/s41598-022-11532-x
Manfredi AA, Ramirez GA, Godino C, Capobianco A, Monno A, Franchini S, Tombetti E, Corradetti S, Distler JH, Bianchi ME, Rovere-Querini P, Maugeri N. Platelet phagocytosis via PSGL1 and accumulation of microparticles in systemic sclerosis. Arthritis Rheumatol. 2021 Jul 19. doi: 10.1002/art.41926.
De Lorenzo R, Sciorati C, Ramirez GA, Colombo B, Lorè NI, Capobianco A, Tresoldi C; Bio Angels for COVID-BioB Study Group, Cirillo DM, Ciceri F, Corti A, Rovere-Querini P, Manfredi AA. Chromogranin A plasma levels predict mortality in COVID-19. PLoS One. 2022 Apr 25;17(4):e0267235. doi: 10.1371/journal.pone.0267235.
Maugeri N, De Lorenzo R, Clementi N, Diotti RA, Criscuolo E, Godino C, Tresoldi C, Bio Angels for COVID-BioB Study Group, Bonini C, Clementi M, Mancini N, Ciceri F, Rovere-Querini P, Manfredi AA. Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19. J Thromb Haemost. 2022 Feb;20(2):434-448. doi: 10.1111/jth.15575.
Lorè NI, De Lorenzo R, Rancoita PMV, Cugnata F, Agresti A, Benedetti F, Bianchi ME, Bonini C, Capobianco A, Conte C, Corti A, Furlan R, Mantegani P, Maugeri N, Sciorati C, Saliu F, Silvestri L, Tresoldi C, Bio Angels for COVID-BioB Study Group, Ciceri F, Rovere-Querini P, Di Serio C, Cirillo DM, Manfredi AA. CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study. Mol Med. 2021 Oct 18;27(1):129. doi: 10.1186/s10020-021-00390-4.
Della-Torre E, Rigamonti E, Perugino C, Baghai-Sain S, Sun N, Kaneko N, Maehara T, Rovati L, Ponzoni M, Milani R, Lanzillotta M, Mahajan V, Mattoo H, Molineris I, Deshpande V, Stone JH, Falconi M, Manfredi AA, Pillai S. B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease. J Allergy Clin Immunol. 2019 Jul 15. pii: S0091-6749(19)30936-4. doi: 10.1016/j.jaci.2019.07.004.
Maugeri N, Capobianco A, Rovere-Querini P, Ramirez GA, Tombetti E, Valle PD, Monno A, D'Alberti V, Gasparri AM, Franchini S, D'Angelo A, Bianchi ME, Manfredi AA. Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis. Sci Transl Med. 2018 Jul 25;10(451).
Della-Torre E, Bozzalla-Cassione E, Sciorati C, Ruggiero E, Lanzillotta M, Bonfiglio S, Mattoo H, Perugino CA, Bozzolo E, Rovati L, Arcidiacono PG, Balzano G, Lazarevic D, Bonini C, Falconi M, Stone JH, Dagna L, Pillai S, Manfredi AA. A CD8α- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment. Arthritis Rheumatol. 2018 Jul;70(7):1133-1143.
Manfredi AA, Ramirez GA, Rovere-Querini P, Maugeri N.The Neutrophil's Choice: Phagocytose vs Make Neutrophil Extracellular Traps. Front Immunol. 2018 Feb 20;9:288.
Manfredi AA, Rovere-Querini P, D'Angelo A, Maugeri N. Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps. Pharmacol Res. 2017 Sep;123:146-156.
Tombetti E, Colombo B, Di Chio MC, Sartorelli S, Papa M, Salerno A, Bozzolo EP, Tombolini E, Benedetti G, Godi C, Lanzani C, Rovere-Querini P, Del Maschio A, Ambrosi A, De Cobelli F, Sabbadini MG, Baldissera E, Corti A, Manfredi AA. Chromogranin-A production and fragmentation in patients with Takayasu arteritis. Arthritis Res Ther. 2016 Aug 17;18:187.
Manfredi AA, Baldini M, Camera M, Baldissera E, Brambilla M, Peretti G, Maseri A, Rovere-Querini P, Tremoli E, Sabbadini MG, Maugeri N. Anti-TNFα agents curb platelet activation in patients with rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1511-20.
Maugeri N, Rovere-Querini P, Baldini M, Baldissera E, Sabbadini MG, Bianchi ME, Manfredi AA. Oxidative stress elicits platelet/leukocyte inflammatory interactions via HMGB1: a candidate for microvessel injury in sytemic sclerosis. Antioxid Redox Signal. 2014 Mar 1;20(7):1060-74.
Bianchi, M.E., Manfredi, A.A. How macrophages ring the inflammation alarm. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 (8), pp. 2866-2867.
Maugeri N, Campana L, Gavina M, Covino C, De Metrio M, Panciroli C, Maiuri L, Maseri A, D'Angelo A, Bianchi ME, Rovere-Querini P, Manfredi AA. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost. 2014 Dec;12(12):2074-88.
