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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

SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination

Daddacha, Waaqo ; Koyen, Allyson E. ; Bastien, Amanda J. ; Head,Pamela Sara E. ; Dhere, Vishal R. ; Nabeta, Geraldine N. ; Connolly, Erin C. ; Werner, Erica ; Madden, Matthew Z. ; Daly, Michele B. ; Minten, Elizabeth V. ; Whelan, Donna R. ; Schlafstein, Ashley J. ; Zhang, Hui ; Anand, Roopesh ; Doronio, Christine ; Withers, Allison E. ; Shepard, Caitlin ; Sundaram, Ranjini K. ; Deng, Xingming ; Dynan, William S. ; Wang, Ya ; Bindra, Ranjit S. ; Cejka, Petr ; Rothenberg, Eli ; Doetsch, Paul W. ; Kim, Baek ; Yu, David S.

In: Cell reports, 2017, vol. 20, no. 8, p. 1921-1935

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV- 1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate...

Università della Svizzera italiana

CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals

Negro, Samuele ; Lessi, Francesca ; Duregotti, Elisa ; Aretini, Paolo ; La Ferla, Marco ; Franceschi, Sara ; Menicagli, Marco ; Bergamin, Elisanna ; Egle, Radice ; Megighian, Aram ; Pirazzini, Marco ; Mazzanti, Chiara M. ; Rigoni, Michela ; Montecucco, Cesare

In: EMBO molecular medicine, 2017, vol. 9, no. 8, p. 1000–1010

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following ...

Università della Svizzera italiana

T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP

Perruzza, Lisa ; Gargari, Giorgio ; Proietti, Michele ; Fosso, Bruno ; D'Erchia, Anna Maria ; Faliti, Caterina Elisa ; Rezzonico-Jost, Tanja ; Scribano, Daniela ; Mauri, Laura ; Colombo, Diego ; Pellegrini, Giovanni ; Moregola, Annalisa ; Mooser, Catherine ; Pesole, Graziano ; Nicoletti, Mauro ; Norata, Giuseppe Danilo ; Geuking, Markus B. ; McCoy, Kathy D. ; Guglielmetti, Simone ; Grassi, Fabio

In: Cell reports, 2017, vol. 18, no. 11, p. 2566-2575

The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer’s patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of...

Università della Svizzera italiana

Influenza vaccination induces NK-cell-mediated type-II IFN response that regulates humoral immunity in an IL-6-dependent manner

Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; Latino, Irene ; Zanaga, Silvia ; Chatziandreou, Nikolaos ; Pizzagalli, Diego Ulisse ; Rinaldi, Andrea ; Bolis, Marco ; Sallusto, Federica ; Stein, Jens V. ; Gonzalez, Santiago F.

In: Cell reports, 2019, vol. 26, no. 9, p. 2307-2315.e5

The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine the function of infiltrated NK cells in the initiation of the inflammatory response triggered by inactivated influenza virus vaccine in the draining lymph node (LN). We observed that, following vaccination, NK cells are recruited to the interfollicular and medullary areas of...

Università della Svizzera italiana

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

Volpi, Vera G. ; Ferri, Cinzia ; Fregno, Ilaria ; Del Carro, Ubaldo ; Bianchi, Francesca ; Scapin, Cristina ; Pettinato, Emanuela ; Solda, Tatiana ; Feltri, M. Laura ; Molinari, Maurizio ; Wrabetz, Lawrence ; D’Antonio, Maurizio

In: PLOS genetics, 2019, vol. 15, no. 4, p. e1008069

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the...

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

HCMV envelope glycoprotein diversity demystified

Foglierini, Mathilde ; Marcandalli, Jessica ; Perez, Laurent

In: Frontiers in microbiology, 2019, vol. 10, p. 1005

Human cytomegalovirus (HCMV) is the leading viral cause of congenital birth defects and is responsible for morbidity and mortality in immunosuppressed individuals. Considerable efforts have been deployed over the last decade to develop a vaccine capable of preventing HCMV infection. However, in recent clinical trials, vaccines showed at best modest efficacy in preventing infection. These...

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...