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Università della Svizzera italiana

The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells

Gonçalves Silva, Isabel ; Yasinska, Inna M. ; Sakhnevych, Svetlana S. ; Fiedler, Walter ; Wellbrock, Jasmin ; Bardelli, Marco ; Varani, Luca ; Hussain, Rohanah ; Siligardi, Giulio ; Ceccone, Giacomo ; Berger, Steffen M. ; Ushkaryov, Yuri A. ; Gibbs, Bernhard F. ; Fasler-Kan, Elizaveta ; Sumbayev, Vadim V.

In: Ebiomedicine, 2017, vol. 22, p. 44-57

Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased...

Università della Svizzera italiana

Epithelial-mesenchymal transition in cancer metastasis through the lymphatic syste

Karlsson, Mikael C. ; Gonzalez, Santiago F. ; Welin, Josefin ; Fuxe, Jonas

In: Molecular oncology, 2017, vol. 11, p. 781–791

It was already in the 18th century when the French surgeon LeDran first noted that breast cancer patients with spread of tumor cells to their axillary lymph nodes had a drastically worse prognosis than patients without spread (LeDran et al., ). Since then, metastatic spread of cancer cells to regional lymph nodes has been established as the most important prognostic factor in many types of...

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

Induction of potent neutralizing antibody responses by a designed protein nanoparticle accine for respiratory syncytial virus

Marcandalli, Jessica ; Fiala, Brooke ; Ols, Sebastian ; Perotti, Michela ; de van der Schueren, Willem ; Snijder, Joost ; Hodge, Edgar ; Benhaim, Mark ; Ravichandran, Rashmi ; Carter, Lauren ; Sheffler, Will ; Brunner, Livia ; Lawrenz, Maria ; Dubois, Patrice ; Lanzavecchia, Antonio ; Sallusto, Federica ; Lee, Kelly K. ; Veesler, David ; Correnti, Colin E. ; Stewart, Lance J. ; Baker, David ; Loré, Karin ; Perez, Laurent ; King, Neil P.

In: Cell, 2019, vol. 177, no. 6, p. 1420-1431.e17

Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein ...

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

PECAM-1 stabilizes blood-brain barrier integrity and favors paracellular T-Cell diapedesis across the blood-brain barrier during neuroinflammation

Wimmer, Isabella ; Tietz, Silvia ; Nishihara, Hideaki ; Deutsch, Urban ; Sallusto, Federica ; Gosselet, Fabien ; Lyck, Ruth ; Muller, William A. ; Lassmann, Hans ; Engelhardt, Britta

In: Frontiers in immunology, 2019, vol. 10, p. 711

Breakdown of the blood-brain barrier (BBB) and increased immune cell trafficking into the central nervous system (CNS) are hallmarks of the pathogenesis of multiple sclerosis (MS). Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is expressed on cells of the vascular compartment and regulates vascular integrity and immune cell trafficking. Involvement of PECAM-1 in MS pathogenesis...

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...