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Public access from 17-ago-2020
Università della Svizzera italiana

Imaging cell interaction in tracheal mucosa during influenza virus infection using two-photon intravital microscopy

Palomino-Segura, Miguel ; Virgilio, Tommaso ; Morone, Diego ; Pizzagalli, Diego U. ; Gonzalez, Santiago F.

In: Journal of visualized experiments, 2018, vol. 138, p. e58355

The analysis of cell-cell or cell-pathogen interaction in vivo is an important tool to understand the dynamics of the immune response to infection. Two-photon intravital microscopy (2P-IVM) allows the observation of cell interactions in deep tissue in living animals, while minimizing the photobleaching generated during image acquisition. To date, different models for 2P-IVM of lymphoid and...

Università della Svizzera italiana

Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides

Bergmann, Timothy J. ; Fregno, Ilaria ; Fumagalli, Fiorenza ; Rinaldi, Andrea ; Bertoni, Francesco ; Boersema, Paul J. ; Picotti, Paola ; Molinari, Maurizio

In: Journal of biological chemistry, 2018, vol. 293, no. 15, p. 5600-5612

The stress sensors ATF6, IRE1, and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to reestablish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans,...

Public access from 30-gen-2020
Università della Svizzera italiana

The contribution of active and passive mechanisms of 5mC and 5hmC removal in human T lymphocytes is differentiation- and activation-dependent

Vincenzetti, Lucia ; Leoni, Cristina ; Chirichella, Michele ; Kwee, Ivo ; Monticelli, Silvia

In: European Journal of Immunology, 2019, p. 1-15

In mammals, the 5’-methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5-hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation...

Università della Svizzera italiana

A selective ER‐phagy exerts procollagen quality control via a Calnexin‐FAM134B complex

Forrester, Alison ; Leonibus, Chiara De ; Grumati, Paolo ; Fasana, Elisa ; Piemontese, Marilina ; Staiano, Leopoldo ; Fregno, Ilaria ; Raimondi, Andrea ; Marazza, Alessandro ; Bruno, Gemma ; Iavazzo, Maria ; Intartaglia, Daniela ; Seczynska, Marta ; van Anken, Eelco ; Conte, Ivan ; De Matteis, Maria Antonietta ; Dikic, Ivan ; Molinari, Maurizio ; Settembre, Carmine

In: The EMBO Journal, 2019, vol. 38, no. 2, p. e99847

Autophagy is a cytosolic quality control process that recognizes substrates through receptor‐mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is...

Università della Svizzera italiana

ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

Proietti, Michele ; Perruzza, Lisa ; Scribano, Daniela ; Pellegrini, Giovanni ; D’Antuono, Rocco ; Strati, Francesco ; Raffaelli, Marco ; Gonzalez, Santiago F. ; Thelen, Marcus ; Hardt, Wolf-Dietrich ; Slack, Emma ; Nicoletti, Mauro ; Grassi, Fabio

In: Nature Communications, 2019, vol. 10, p. Art. number: 250

T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells...

Università della Svizzera italiana

The motor activity of DNA2 functions as an ssDNA translocase to promote DNA end resection

Levikova, Maryna ; Pinto, Cosimo ; Cejka, Petr

In: Genes and Development, 2017, vol. 31, no. 5, p. 493-502

DNA2 nuclease–helicase functions in DNA replication and recombination. This requires the nuclease of DNA2, while, in contrast, the role of the helicase activity has been unclear. We now show that the motor activity of both recombinant yeast and human DNA2 promotes efficient degradation of long stretches of ssDNA, particularly in the presence of the replication protein A. This degradation is...

Università della Svizzera italiana

P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus

Faliti, Caterina E. ; Gualtierotti, Roberta ; Rottoli, Elsa ; Gerosa, Maria ; Perruzza, Lisa ; Romagnani, Andrea ; Pellegrini, Giovanni ; De Ponte Conti, Benedetta ; Rossi, Riccardo L. ; Idzko, Marco ; Mazza, Emilia M.C. ; Bicciato, Silvio ; Traggiai, Elisabetta ; Meroni, Pier Luigi ; Grassi, Fabio

In: Journal of Experimental Medicine, 2019, vol. 216, no. 2, p. 317-336

Altered control of T follicular helper (Tfh) cells can lead to generation of autoantibodies and autoimmune manifestations. Signaling pathways that selectively limit pathogenic responses without affecting the protective function of Tfh cells are unknown. Here we show that the ATP-gated ionotropic P2X7 receptor restricts the expansion of aberrant Tfh cells and the generation of self-reactive...

Università della Svizzera italiana

Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection

Reginato, Giordano ; Cannavo, Elda ; Cejka, Petr

In: Genes and Development, 2017, vol. 31, no. 23-24, p. 2325-2330

DNA double-strand break repair by homologous recombination is initiated by DNA end resection, which is commenced by the Mre11–Rad50–Xrs2 complex and Sae2 in yeast. Here we report that the nonhomologous end joining factor Ku limits the exonuclease activity of Mre11 and promotes its endonuclease to cleave 5'-terminated DNA strands at break sites. Following initial endonucleolytic cleavage...

Public access from 15-gen-2021
Università della Svizzera italiana

Modelling protein-protein interactions to elucidate molecular mechanisms behind neurodegenerative diseases

Grasso, Gianvito ; Krause, Rolf (Dir.) ; Danani, Andrea (Codir.)

Thèse de doctorat : Università della Svizzera italiana, 2018 ; 2018INFO017.

The worldwide significant increase in life expectancy has recently drawn the attention of the scientific community to neurodegenerative pathologies of the elderly population. These neurodegenerative disorders arise from the abnormal protein aggregation in the nervous tissue leading to intracellular inclusions or extracellular aggregates in specific brain areas. A feasible strategy to prevent...

Università della Svizzera italiana

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Markle, Janet G. ; Martínez-Barricarte, Rubén ; Ma, Cindy S. ; Deenick, Elissa K. ; Ramírez-Alejo, Noé ; Mele, Federico ; Latorre, Daniela ; Mahdaviani, Seyed Alireza ; Aytekin, Caner ; Mansouri, Davood ; Bryant, Vanessa L. ; Jabot-Hanin, Fabienne ; Deswarte, Caroline ; Nieto-Patlán, Alejandro ; Surace, Laura ; Kerner, Gaspard ; Itan, Yuval ; Jovic, Sandra ; Avery, Danielle T. ; Wong, Natalie ; Rao, Geetha ; Patin, Etienne ; Okada, Satoshi ; Bigio, Benedetta ; Boisson, Bertrand ; Rapaport, Franck ; Seeleuthner, Yoann ; Schmidt, Monika ; Ikinciogullari, Aydan ; Dogu, Figen ; Tanir, Gonul ; Tabarsi, Payam ; Bloursaz, Mohammed Reza ; Joseph, Julia K. ; Heer, Avneet ; Kong, Xiao-Fei ; Migaud, Mélanie ; Lazarov, Tomi ; Geissmann, Frédéric ; Fleckenstein, Bernhard ; Lindestam Arlehamn, Cecilia ; Sette, Alessandro ; Puel, Anne ; Emile, Jean-François ; Vosse, Esther van de ; Quintana-Murci, Lluis ; Di Santo, James P. ; Abel, Laurent ; Boisson-Dupuis, Stéphanie ; Bustamante, Jacinta ; Tangye, Stuart G. ; Sallusto, Federica ; Casanova, Jean-Laurent

In: Science Immunology, 2018, vol. 3, no. 30, p. eaau6759

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity,...