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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

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

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

ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells

Mele, Federico ; Basso, Camilla ; Leoni, Cristina ; Aschenbrenner, Dominik ; Becattini, Simone ; Latorre, Daniela ; Lanzavecchia, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Nature communications, 2015, vol. 6, p. 6431

T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a...

Università della Svizzera italiana

Rationally modified estrogen receptor protein as a bio-recognition element for the detection of EDC pollutants : strategies and opportunities

Pedotti, Mattia ; Ferrero, Valentina Elisabetta Viviana ; Lettieri, Teresa ; Colpo, Pascal ; Follonier, Stephane ; Calzolai, Luigi ; Varani, Luca

In: International journal of environmental research and public health, 2015, vol. 12, no. 3, p. 2612-2621

The estrogen receptor protein (ER) can bind a vast number of organic pollutants widely spread in the environment and collectively known as Endocrine Disrupting Chemicals, EDCs. Its broad selectivity makes it an ideal bio-recognition element for the detection of EDCs. Here we describe the strategy and rationale for the design of ER based biosensors and assays that generate a signal in the...

Università della Svizzera italiana

Rag defects and thymic stroma : lessons from animal models

Marrella, Veronica ; Poliani, Pietro Luigi ; Notarangelo, Luigi Daniele ; Grassi, Fabio ; Villa, Anna

In: Frontiers in immunology, 2014, vol. 5, p. 259

Thymocytes and thymic epithelial cells (TECs) cross-talk is essential to support T cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that...

Università della Svizzera italiana

Rational modification of estrogen receptor by combination of computational and experimental analysis

Ferrero, Valentina Elisabetta Viviana ; Pedotti, Mattia ; Chiadò, Alessandro ; Simonelli, Luca ; Calzolai, Luigi ; Varani, Luca ; Lettieri, Teresa

In: Plos one, 2014, vol. 9, no. 7, p. e102658

In this manuscript, we modulate the binding properties of estrogen receptor protein by rationally modifying the amino acid composition of its ligand binding domain. By combining sequence alignment and structural analysis of known estrogen receptor- ligand complexes with computational analysis, we were able to predict estrogen receptor mutants with altered binding properties. These predictions...

Università della Svizzera italiana

Rational engineering of a human anti-dengue antibody through experimentally validated computational docking

Simonelli, Luca ; Pedotti, Mattia ; Beltramello, Martina ; Livoti, Elsa ; Calzolai, Luigi ; Sallusto, Federica ; Lanzavecchia, Antonio ; Varani, Luca

In: Plos one, 2013, vol. 8, no. 2, p. e55561

Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and ...

Università della Svizzera italiana

CCR2 acts as scavenger for CCL2 during monocyte chemotaxis

Volpe, Silvia ; Cameroni, Elisabetta ; Moepps, Barbara ; Thelen, Sylvia ; Apuzzo, Tiziana ; Thelen, Marcus

In: Plos one, 2012, vol. 7, no. 5, p. e37208

Background: Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces...