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Università della Svizzera italiana

Quality control mechanisms of protein biogenesis : proteostasis dies hard

Bergmann, Timothy Jan ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478

The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...

Università della Svizzera italiana

Post ER quality control : a role for UDP-glucose : glycoprotein glucosyl transferase and p97

Fregno, Ilaria ; Molinari, Maurizio

In: Journal of rare diseases research & treatment, 2016, vol. 1, no. 1, p. 40-42

Human proteinopathies are diseases caused by the expression of defective gene products. In some cases, these diseases involve the degradation of mutant but otherwise functional proteins by the quality control system of the secretory pathway. Our recent study identified two proteins that play a role in post-endoplasmic reticulum (ER) quality control and are potential targets for therapeutic ...

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

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

Montagner, Sara ; Leoni, Cristina ; Emming, Stefan ; Della Chiara, Giulia ; Balestrieri, Chiara ; Barozzi, Iros ; Piccolo, Viviana ; Togher, Susan ; Ko, Myunggon ; Rao, Anjana ; Natoli, Gioacchino ; Monticelli, Silvia

In: Cell reports, 2016, vol. 15, no. 7, p. 1566-1579

Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC). Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of...

Università della Svizzera italiana

Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis

De Benedictis, Paola ; Minola, Andrea ; Rota Nodari, Elena ; Aiello, Roberta ; Zecchin, Barbara ; Salomoni, Angela ; Foglierini, Mathilde ; Agatic, Gloria ; Vanzetta, Fabrizia ; Lavenir, Rachel ; Lepelletier, Anthony ; Bentley, Emma ; Weiss, Robin ; Cattoli, Giovanni ; Capua, Ilaria ; Sallusto, Federica ; Wright, Edward ; Lanzavecchia, Antonio ; Bourhy, Hervé ; Corti, Davide

In: EMBO molecular medicine, 2016, vol. 8, no. 4, p. 407-421

Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a...

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

Metainference : a Bayesian inference method for heterogeneous systems

Bonomi, Massimiliano ; Camilloni, Carlo ; Cavalli, Andrea ; Vendruscolo, Michele

In: Science advances, 2016, vol. 2, no. 1, p. e1501177

Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, especially when a system simultaneously populates an ensemble of different...

Università della Svizzera italiana

Epigenetics of T lymphocytes in health and disease

Leoni, Cristina ; Vincenzetti, Lucia ; Emming, Stefan ; Monticelli, Silvia

In: Swiss Medical weekly, 2015, vol. 145, p. w14191

The risk of developing autoimmune diseases depends on both genetic and environmental factors, with epigenetic mechanisms of regulation potentially translating environmental cues into stable modifications in gene expression. Such stable memory of a functional state has been deciphered into a number of molecular mechanisms that collectively define the epigenetic status of a cell. In recent years,...

Università della Svizzera italiana

Antigen-specific Th17 cells are primed by distinct and complementary dendritic cell subsets in oropharyngeal candidiasis

Trautwein-Weidner, Kerstin ; Gladiator, André ; Kirchner, Florian R. ; Becattini, Simone ; Rülicke, Thomas ; Sallusto, Federica ; LeibundGut-Landmann, Salomé

In: PLoS pathogens, 2015, vol. 11, no. 10, p. e1005164

Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated...