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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

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...

Università della Svizzera italiana

Within-host evolution results in antigenically distinct GII.4 noroviruses

Debbink, Kari ; Lindesmith, Lisa C. ; Ferris, Martin T. ; Swanstrom, Jesica ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Journal of virology, 2014, vol. 88, no. 13, p. 7244–7255

Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic...

Università della Svizzera italiana

Earthquakes, grants and public expenditure : how municipalities respond to natural disasters

Masiero, Giuliano ; Santarossa, Michael

We analyze the response of municipalities to the occurrence of natural disasters (earthquakes) in Italy, in terms of spending behavior, use of upper tier transfers and recovery. We find evidence of increasing expenditure for about 12 years after the shock, with asymmetric responses between matching (earthquake-related) and unconditional grants, and heterogeneous flypaper effects across the...

Università della Svizzera italiana

Proteome-wide analysis of HIV-specific naive and memory CD4+ T cells in unexposed blood donors

Campion, Suzanne L. ; Brodie, Tess M. ; Fischer, William ; Korber, Bette T. ; Rossetti, Astrea ; Goonetilleke, Nilu ; McMichael, Andrew J. ; Sallusto, Federica

In: Journal of experimental medicine, 2014, vol. 211, no. 7, p. 1273-1280

The preexisting HIV-1–specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4+ T cell repertoire in healthy HIV-1–negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the...

Università della Svizzera italiana

Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation

Takizawa, Hitoshi ; Regoes, Roland R. ; Boddupalli, Chandra S. ; Bonhoeffer, Sebastian ; Manz, Markus G.

In: Journal of experimental medicine, 2011, vol. 208, no. 2, p. 273-284

Hematopoietic stem cells (HSCs) maintain blood production. How often mouse HSCs divide and whether each HSC contributes simultaneously, sequentially, or repetitively to hematopoiesis remains to be determined. We track division of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeled HSC in vivo. We found that, in steady-state mice, bone marrow cells capable of...