Immunology, Transplantation and Infectious diseases
Autoimmunity and vascular inflammation
Inflammation is a homeostatic process triggered by microbial components and tissue damage. The ways in which the cells die, the cellular constituents reach the extracellular environment and are recognized by the cells of the immune system determine the effects of the inflammatory response in terms of:
- tissue repair,
- inflammatory damage that becomes chronic and self-sustaining.
Alterations in the early and late phases of the process, in particular in the phagocytic clearance of dead cells and debris, play a key role in systemic autoimmune diseases, wherein the altered response to these signals plays a role in both disease origin and in the amplification mechanism and acceleration of clinical features determining the specific characteristics of each disease. Persiste vascular inflammation, in particular, reflects a vicious circle through which inflammatory leucocytes are attracted and activate in the walls of the vessels that they further damage. Restoration of the regulatory network of signals that connect leucocytes, platelets and endothelial cells might be valuable to limit the noxious 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 Alarmine) and humoral innate immunity.
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, 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.
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.
Maugeri N, Rovere-Querini P, Slavich M, Coppi G, Doni A, Bottazzi B, Garlanda C, Cianflone D, Maseri A, Mantovani A, Manfredi AA. Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction. J Immunol. 2011 Jul 15;187(2):970-9.
