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Università della Svizzera italiana

Dissecting human antibody responses: useful, basic and surprising findings

Lanzavecchia, Antonio

In: EMBO molecular medicine, 2018, vol. 10, p. e8879

Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells...

Università della Svizzera italiana

New insights in chemokine signaling

Legler, Daniel F. ; Thelen, Marcus

In: F1000Research, 2018, vol. 7, p. 95

Chemokine signaling is essential for coordinated cell migration in health and disease to specifically govern cell positioning in space and time. Typically, chemokines signal through heptahelical, G protein-coupled receptors to orchestrate cell migration. Notably, chemokine receptors are highly dynamic structures and signaling efficiency largely depends on the discrete contact with the ligand....

Università della Svizzera italiana

Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells

Niogret, Charlène ; Miah, S. M. Shahjahan ; Rota, Giorgia ; Fonta, Nicolas P. ; Wang, Haiping ; Held, Werner ; Birchmeier, Walter ; Sexl, Veronica ; Yang, Wentian ; Vivier, Eric ; Ho, Ping-Chih ; Brossay, Laurent ; Guarda, Greta

In: Nature communications, 2019, vol. 10, p. 1444

The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to...

Università della Svizzera italiana

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

Ranjha, Lepakshi ; Levikova, Maryna ; Altmannova, Veronika ; Krejci, Lumir ; Cejka, Petr

In: Communications Biology, 2019, vol. 2, p. 174

Dna2 is an essential nuclease-helicase that acts in several distinct DNA metabolic pathways including DNA replication and recombination. To balance these functions and prevent unscheduled DNA degradation, Dna2 activities must be regulated. Here we show that Saccharomyces cerevisiae Dna2 function is controlled by sumoylation. We map the sumoylation sites to the N-terminal regulatory domain of...

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

Enrichment of intestinal Lactobacillus by enhanced secretory IgA coating alters glucose homeostasis in P2rx7-/- mice

Perruzza, Lisa ; Strati, Francesco ; Gargari, Giorgio ; D’Erchia, Anna Maria ; Fosso, Bruno ; Pesole, Graziano ; Guglielmetti, Simone ; Grassi, Fabio

In: Scientific reports, 2019, vol. 9, p. 9315

The secretory immunoglobulin A (SIgA) in mammalian gut protects the organism from infections and contributes to host physiology by shaping microbiota composition. The mechanisms regulating the adaptive SIgA response towards gut microbes are poorly defined. Deletion of P2rx7, encoding for the ATP-gated ionotropic P2X7 receptor, leads to T follicular helper (Tfh) cells expansion in the Peyer’s...

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

Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

Ronchi, Francesca ; Basso, Camilla ; Preite, Silvia ; Reboldi, Andrea ; Baumjohann, Dirk ; Perlini, Luana ; Lanzavecchia, Antonio ; Sallusto, Federica

In: Nature communications, 2016, vol. 7, p. 11541

CD4+ Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORγt and T-bet and producing IL-17A, IFN-γ and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the...

Università della Svizzera italiana

The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae

Engen, Stian André ; Rukke, Håkon Valen ; Becattini, Simone ; Jarrossay, David ; Blix, Inger Johanne ; Petersen, Fernanda Cristina ; Sallusto, Federica ; Schenck, Karl

In: Plos one, 2017, vol. 9, no. 8, p. e104306

Background: Carriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized. Methods: Memory CD4+ T helper (Th) cell subsets were isolated from...

Università della Svizzera italiana

Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers

Taglialatela, Angelo ; Alvarez, Silvia ; Leuzzi, Giuseppe ; Sannino, Vincenzo ; Ranjha, Lepakshi ; Huang, Jen-Wei ; Madubata, Chioma ; Anand, Roopesh ; Levy, Brynn ; Rabadan, Raul ; Cejka, Petr ; Costanzo, Vincenzo ; Ciccia, Alberto

In: Molecular Cell, 2017, vol. 68, no. 2, p. 414-430.e8

To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a...