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Università della Svizzera italiana

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Willinger, Tim ; Rongvaux, Anthony ; Takizawa, Hitoshi ; Yancopoulos, George D. ; Valenzuela, David M. ; Murphy, Andrew J. ; Auerbach, Wojtek ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2390-2395

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and...

Università della Svizzera italiana

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

Rongvaux, Anthony ; Willinger, Tim ; Takizawa, Hitoshi ; Rathinam, Chozhavendan ; Auerbach, Wojtek ; Murphy, Andrew J. ; Valenzuela, David M. ; Yancopoulos, George D. ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2378-2383

Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial...

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...

Università della Svizzera italiana

Activin-A co-opts IRF4 and AhR signaling to induce human regulatory T cells that restrain asthmatic responses

Tousa, Sofia ; Semitekolou, Maria ; Morianos, Ioannis ; Banos, Aggelos ; Trochoutsou, Aikaterini I. ; Brodie, Tess M. ; Poulos, Nikolaos ; Samitas, Konstantinos ; Kapasa, Maria ; Konstantopoulos, Dimitris ; Paraskevopoulos, Giannis ; Gaga, Mina ; Hawrylowicz, Catherine M. ; Sallusto, Federica ; Xanthou, Georgina

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 14, p. E2891-E2900

Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4+ T cells that express the...

Università della Svizzera italiana

Ectonucleotidase activity and immunosuppression in astrocyte-CD4 T cell bidirectional signaling

Filipello, Fabia ; Pozzi, Davide ; Proietti, Michele ; Romagnani, Andrea ; Mazzitelli, Sonia ; Matteoli, Michela ; Verderio, Claudia ; Grassi, Fabio

In: Oncotarget, 2016, vol. 7, no. 5, p. 5143-5156

Astrocytes play a crucial role in neuroinflammation as part of the glia limitans, which regulates infiltration of the brain parenchyma by leukocytes. The signaling pathways and molecular events, which result from the interaction of activated T cells with astrocytes are poorly defined. Here we show that astrocytes promote the expression and enzymatic activity of CD39 and CD73 ectonucleotidases in...

Università della Svizzera italiana

Dnmt3a restrains mast cell inflammatory responses

Leoni, Cristina ; Montagner, Sara ; Rinaldi, Andrea ; Bertoni, Francesco ; Polletti, Sara ; Balestrieri, Chiara ; Monticelli, Silvia

In: Proceedings of the national academy of sciences, 2017, vol. 114, no. 8, p. E1490-E1499

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using...

Università della Svizzera italiana

Chemokines : chemistry, biochemistry and biological function

Legler, Daniel F. ; Thelen, Marcus

In: Chimia : International journal for chemistry, 2016, vol. 70, no. 12, p. 856-859

The in vitro synthesis of correctly folded functional proteins remains challenging. Chemokines, which consist of only 70–100 amino acids, are accessible through solid- phase synthesis and easily fold into a thermally stable tertiary structure. From the time of their discovery in the late 1980s chemokines could therefore be synthesized using biochemical and chemical protocols for...

Università della Svizzera italiana

High performance selected inversion methods for sparse matrices : direct and stochastic approaches to selected inversion

Verbosio, Fabio ; Schenk, Olaf (Dir.)

Thèse de doctorat : Università della Svizzera italiana, 2019 ; 2019INFO002.

The explicit evaluation of selected entries of the inverse of a given sparse matrix is an important process in various application fields and is gaining visibility in recent years. While a standard inversion process would require the computation of the whole inverse who is, in general, a dense matrix, state-of-the-art solvers perform a selected inversion process instead. Such approach allows...

Università della Svizzera italiana

Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle

Cavalli, Andrea ; Camilloni, Carlo ; Vendruscolo, Michele

In: The journal of chemical physics, 2013, vol. 138, no. 9, p. 094112

In order to characterise the dynamics of proteins, a well-established method is to incorporate experimental parameters as replica-averaged structural restraints into molecular dynamics simulations. Here, we justify this approach in the case of interproton distance information provided by nuclear Overhauser effects by showing that it generates ensembles of conformations according to the maximum...

Università della Svizzera italiana

CXCR7 prevents excessive CXCL12-mediated downregulation of CXCR4 in migrating cortical interneurons

Abe, Philipp ; Mueller, Wiebke ; Schütz, Dagmar ; MacKay, Fabienne ; Thelen, Marcus ; Zhang, Penglie ; Stumm, Ralf

In: Development, 2014, vol. 141, no. 9, p. 1857-1863

The CXCL12/CXCR4 signaling pathway is involved in the development of numerous neuronal and non-neuronal structures. Recent work established that the atypical second CXCL12 receptor, CXCR7, is essential for the proper migration of interneuron precursors in the developing cerebral cortex. Two CXCR7-mediated functions were proposed in this process: direct modulation of β-arrestin-mediated...