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Università della Svizzera italiana

LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity

Bertelli, Roberta ; Di Donato, Armando ; Cioni, Michela ; Grassi, Fabio ; Ikehata, Masami ; Bonanni, Alice ; Rastaldi, Maria Pia ; Ghiggeri, Gian Marco

In: Plos one, 2014, vol. 9, no. 10, p. e111285

Immunosuppressive regulatory T cells (Tregs) have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna) and/or drug induced (Adriamycin) nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg) was given as single shot in C57BL/6,...

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

Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection

Lilleri, Daniele ; Kabanova, Anna ; Revello, Maria Grazia ; Percivalle, Elena ; Sarasini, Antonella ; Genini, Emilia ; Sallusto, Federica ; Lanzavecchia, Antonio ; Corti, Davide ; Gerna, Giuseppe

In: Plos one, 2013, vol. 8, no. 3, p. e59863

Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and...

Università della Svizzera italiana

Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface

Di Zenzo, Giovanni ; Di Lullo, Giulia ; Corti, Davide ; Calabresi, Valentina ; Sinistro, Anna ; Vanzetta, Fabrizia ; Didona, Biagio ; Cianchini, Giuseppe ; Hertl, Michael ; Eming, Rudiger ; Amagai, Masayuki ; Ohyama, Bungo ; Hashimoto, Takashi ; Sloostra, Jerry ; Sallusto, Federica ; Zambruno, Giovanna ; Lanzavecchia, Antonio

In: The journal of clinical investigation, 2012, vol. 122, no. 10, p. 3781-3790

Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3 and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3 from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro,...

Università della Svizzera italiana

HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- gamma c-/- Mice

Villaudy, Julien ; Wencker, Mélanie ; Gadot, Nicolas ; Gillet, Nicolas A. ; Scoazec, Jean-Yves ; Gazzolo, Louis ; Manz, Markus G. ; Bangham, Charles R. M. ; Duc Dodon, Madeleine

In: Plos pathogens, 2011, vol. 7, no. 9, p. e1002231

Alteration of early haematopoietic development is thought to be responsible for the onset of immature leukemias and lymphomas. We have previously demonstrated that TaxHTLV-1 interferes with ß- selection, an important checkpoint of early thymopoiesis, indicating that human T-cell leukemia virus type 1 (HTLV-1) infection has the potential to perturb thymic human αβ T-cell development. To...

Università della Svizzera italiana

Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects

Rigoni, Rosita ; Fontana, Elena ; Guglielmetti, Simone ; Fosso, Bruno ; D’Erchia, Anna Maria ; Maina, Virginia ; Taverniti, Valentina ; Carmina Castiello, Maria ; Mantero, Stefano ; Pacchiana, Giovanni ; Musio, Silvia ; Pedotti, Rosetta ; Selmi, Carlo ; Mora, J. Rodrigo ; Pesole, Graziano ; Vezzoni, Paolo ; Poliani, Pietro Luigi ; Grassi, Fabio ; Villa, Anna ; Cassani, Barbara

In: The journal of experimental medicine, 2016, vol. 213, no. 3, p. 355-375

Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated. Here, we show that Rag2R229Q knock-in mice developed an inflammatory bowel disease affecting...

Università della Svizzera italiana

miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

Rusca, Nicole ; Dehò, Lorenzo ; Montagner, Sara ; Zielinski, Christina E. ; Sica, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Molecular and cellular biology, 2012, vol. 32, no. 21, p. 4432-4444

The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell...

Università della Svizzera italiana

Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies

Kabanovaa, Anna ; Perez, Laurent ; Lilleri, Daniele ; Marcandalli, Jessica ; Agatic, Gloria ; Becattini, Simone ; Preite, Silvia ; Fuschillo, Dario ; Percivalle,Elena ; Sallusto, Federica ; Gerna, Giuseppe ; Corti, Davide ; Lanzavecchia, Antonio

In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970

The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...

Università della Svizzera italiana

Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc −/− mice improves engraftment of human hematopoietic cells in humanized mice

Strowig, Till ; Rongvaux, Anthony ; Rathinam, Chozhavendan ; Takizawa, Hitoshi ; Borsotti, Chiara ; Philbrick, William ; Eynon, Elizabeth E. ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 32, p. 13218-13223

Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development of a human hematopoietic and immune system in vivo. NOD/scid/γc−/− (NSG) and BALB/c Rag2−/ −γc−/− mice are the most commonly used mouse strains for this purpose and a number of studies have demonstrated the high value of these model systems in areas spanning from...

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...