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Université de Fribourg

β-Arrestin1 and β-Arrestin2 are required to support the activity of the CXCL12/HMGB1 heterocomplex on CXCR4

D’Agostino, Gianluca ; Artinger, Marc ; Locati, Massimo ; Perez, Laurent ; Legler, Daniel F. ; Bianchi, Marco E. ; Rüegg, Curzio ; Thelen, Marcus ; Marchese, Adriano ; Rocchi, Marco B. L. ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in Immunology, 2020, vol. 11, p. -

The chemokine receptor CXCR4 plays a fundamental role in homeostasis and pathology by orchestrating recruitment and positioning of immune cells, under the guidance of a CXCL12 gradient. The ability of chemokines to form heterocomplexes, enhancing their function, represents an additional level of regulation on their cognate receptors. In particular, the multi-faceted activity of the...

Università della Svizzera italiana

Molecular signatures of immunity and immunogenicity in infection and vaccination

Haks, Mariëlle C. ; Bottazzi, Barbara ; Cecchinato, Valentina ; De Gregorio, Corinne ; Del Giudice, Giuseppe ; Kaufmann, Stefan H. E. ; Lanzavecchia, Antonio ; Lewis, David J. M. ; Maertzdorf, Jeroen ; Mantovani, Alberto ; Sallusto, Federica ; Sironi, Marina ; Uguccioni, Mariagrazia ; Ottenhoff, Tom H. M.

In: Frontiers in immunology, 2017, vol. 8, p. 1563

Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable...

Università della Svizzera italiana

Oxidation state dependent conformational changes of HMGB1 regulate the formation of the CXCL12/HMGB1 heterocomplex

Fassi, Enrico M.A. ; Sgrignani, Jacopo ; D'Agostino, Gianluca ; Cecchinato, Valentina ; Garofalo, Maura ; Grazioso, Giovanni ; Uguccioni, Mariagrazia ; Cavalli, Andrea

In: Computational and structural biotechnology journal, 2019, vol. 17, p. 886-894

High-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively via the chemokine receptor CXCR4 enhancing leukocyte recruitment. Here, we used...

Università della Svizzera italiana

Macrophage death following influenza vaccination initiates the inflammatory response that promotes dendritic cell function in the draining lymph node

Chatziandreou, Nikolaos ; Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; D’Antuono, Rocco ; Pizzagalli, Diego Ulisse ; Sallusto, Federica ; Lukacs-Kornek, Veronika ; Uguccioni, Mariagrazia ; Corti, Davide ; Turley, Shannon J. ; Lanzavecchia, Antonio ; Carroll, Michael C. ; Gonzalez, Santiago F.

In: Cell reports, 2017, vol. 18, no. 10, p. 2427-2440

The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7)...

Università della Svizzera italiana

Modulation of chemokine responses : synergy and cooperativity

Proudfoot, Amanda E.I. ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2016, vol. 7, p. 183

Chemokine biology is mediated by more complex interactions than simple monomolecular ligand–receptor interactions, as chemokines can form higher order quaternary structures, which can also be formed after binding to glycosaminoglycans (GAGs) on endothelial cells, and their receptors are found as dimers and/or oligomers at the cell surface. Due to the complexity of the chemokine binding and...

Università della Svizzera italiana

Potential of PEGylated toll-like receptor 7 ligands for controlling inflammation and functional changes in mouse models of asthma and silicosis

Teixeira Ferreira, Tatiana Paula ; Lacerda Mariano, Lívia ; Ghilosso-Bortolini, Roberta ; Santos de Arantes, Ana Carolina ; Fernandes, Andrey Junior ; Berni, Michelle ; Cecchinato, Valentina ; Uguccioni, Mariagrazia ; Maj, Roberto ; Barberis, Alcide ; Machado Rodrigues Silva, Patricia ; Martins, Marco Aurélio

In: Frontiers in immunology, 2016, vol. 7, p. 95

Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim...

Università della Svizzera italiana

Chemokine heterocomplexes and cancer : A novel chapter to be written in tumor immunity

D'Agostino, Gianluca ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2185

Infiltrating immune cells are a key component of the tumor microenvironment and play central roles in dictating tumor fate, either promoting anti-tumor immune responses, or sustaining tumor growth, angiogenesis and metastasis. A distinctive microenvironment is often associated to different tumor types, with substantial differences in prognosis. The production of a variety of chemotactic...

Università della Svizzera italiana

Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis

Cecchinato, Valentina ; D'Agostino, Gianluca ; Raeli, Lorenzo ; Nerviani, Alessandra ; Schiraldi, Milena ; Danelon, Gabriela ; Manzo, Antonio ; Thelen, Marcus ; Ciurea, Adrian ; Bianchi, Marco E. ; Rubartelli, Anna ; Pitzalis, Costantino ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2118

Chemokine synergy-inducing molecules are emerging as regulating factors in cell migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12 enhancing its activity on monocytes via the chemokine receptor CXCR4, while the form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade of events leading to production of cytokines and chemokines. So far, the...

Università della Svizzera italiana

Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Venereau, Emilie ; Casalgrandi, Maura ; Schiraldi, Milena ; Antoine, Daniel J. ; Cattaneo, Angela ; De Marchis, Francesco ; Liu, Jaron ; Antonelli, Antonella ; Preti, Alessandro ; Raeli, Lorenzo ; Samadi Shams, Sara ; Yang, Huan ; Varani, Luca ; Andersson, Ulf ; Tracey, Kevin J. ; Bachi, Angela ; Uguccioni, Mariagrazia ; Bianchi, Marco E.

In: The journal of experimental medicine, 2012, vol. 209, no. 9, p. 1519-1528

Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to...