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.
Nicolosi PA, Tombetti E, Giovenzana A, Donè E, Pulcinelli E, Meneveri R, Tirone M, Maugeri N, Rovere-Querini P, Manfredi AA, Brunelli S. Macrophages Guard Endothelial Lineage by Hindering Endothelial-to-Mesenchymal Transition: Implications for the Pathogenesis of Systemic Sclerosis. J Immunol. 2019 Jul 1;203(1):247-258.
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).
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.
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, 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.
Cottone L, Capobianco A, Gualteroni C, Monno A, Raccagni I, Valtorta S, Canu T, Di Tomaso T, Lombardo A, Esposito A, Moresco RM, Maschio AD, Naldini L, Rovere-Querini P, Bianchi ME, Manfredi AA. Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. Oncoimmunology 2016 Jan 8;5(5):e1122860.
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.
Cottone L, Capobianco A, Gualteroni C, Perrotta C, Bianchi ME, Rovere-Querini P, Manfredi AA. 5-Fluorouracil causes leukocytes attraction in the peritoneal cavity by activating autophagy and HMGB1 release in colon carcinoma cells. Int J Cancer. 2015 Mar 15;136(6):1381-9.
Tombetti E, Di Chio MC, Sartorelli S, Papa M, Salerno A, Bottazzi B, Bozzolo EP, Greco M, Rovere-Querini P, Baldissera E, Del Maschio A, Mantovani A, De Cobelli F, Sabbadini MG, Manfredi AA. Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis. Arthritis Res Ther. 2014 Nov 14;16(6):479.
Ramirez GA, Lanzani C, Bozzolo EP, Citterio L, Zagato L, Casamassima N, Canti V, Sabbadini MG, Rovere-Querini P, Manunta P, Manfredi AA. TRPC6 gene variants and neuropsychiatric lupus. J Neuroimmunol. 2015 Nov 15;288:21-4.
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.
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.
Baldini M, Maugeri N, Ramirez GA, Giacomassi C, Castiglioni A, Prieto-González S, Corbera-Bellalta M, Di Comite G, Papa I, Dell'antonio G, Ammirati E, Cuccovillo I, Vecchio V, Mantovani A, Rovere-Querini P, Sabbadini MG, Cid MC, Manfredi AA. Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia. Arthritis Rheum. 2012 Mar;64(3):854-65.
Maugeri N, Malato S, Femia EA, Pugliano M, Campana L, Lunghi F, Rovere-Querini P, Lussana F, Podda G, Cattaneo M, Ciceri F, Manfredi AA. Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia. Blood 2011 Sep 22;118(12):3359-66.
