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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

Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity

Schena, Francesca ; Volpi, Stefano ; Faliti, Caterina Elisa ; Penco, Federica ; Santi, Spartaco ; Proietti, Michele ; Schenk, Ursula ; Damonte, Gianluca ; Salis, Annalisa ; Bellotti, Marta ; Fais, Franco ; Tenca, Claudya ; Gattorno, Marco ; Eibel, Hermann ; Rizzi, Marta ; Warnatz, Klaus ; Idzko, Marco ; Ayata, Cemil Korcan ; Rakhmanov, Mirzokhid ; Galli, Thierry ; Martini, Alberto ; Canossa, Marco ; Grassi, Fabio ; Traggiai, Elisabetta

In: Cell report, 2013, vol. 3, no. 6, p. 1824-1831

Immunoglobulin (Ig) isotype diversification by class switch recombination (CSR) is an essential process for mounting a protective humoral immune response. Ig CSR deficiencies in humans can result from an intrinsic B cell defect; however, most of these deficiencies are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID). Here, we show that extracellular...

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

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

Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome

Cassani, Barbara ; Poliani, Pietro Luigi ; Marrella, Veronica ; Schena, Francesca ; Sauer, Aisha V. ; Ravanini, Maria ; Strina, Dario ; Busse, Christian E. ; Regenass, Stephan ; Wardemann, Hedda ; Martini, Alberto ; Facchetti, Fabio ; Burg, Mirjam van der ; Rolink, Antonius G. ; Vezzoni, Paolo ; Grassi, Fabio ; Traggiai, Elisabetta ; Villa, Anna

In: Journal of experimental medicine, 2010, vol. 207, no. 7, p. 1525-1540

Hypomorphic RAG mutations, leading to limited V(D)J rearrangements, cause Omenn syndrome (OS), a peculiar severe combined immunodeficiency associated with autoimmune-like manifestations. Whether B cells play a role in OS pathogenesis is so far unexplored. Here we report the detection of plasma cells in lymphoid organs of OS patients, in which circulating B cells are undetectable. Hypomorphic...

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

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

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

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...