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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

T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP

Perruzza, Lisa ; Gargari, Giorgio ; Proietti, Michele ; Fosso, Bruno ; D'Erchia, Anna Maria ; Faliti, Caterina Elisa ; Rezzonico-Jost, Tanja ; Scribano, Daniela ; Mauri, Laura ; Colombo, Diego ; Pellegrini, Giovanni ; Moregola, Annalisa ; Mooser, Catherine ; Pesole, Graziano ; Nicoletti, Mauro ; Norata, Giuseppe Danilo ; Geuking, Markus B. ; McCoy, Kathy D. ; Guglielmetti, Simone ; Grassi, Fabio

In: Cell reports, 2017, vol. 18, no. 11, p. 2566-2575

The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer’s patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of...

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

TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut

Romagnani, Andrea ; Vettore, Valentina ; Rezzonico-Jost, Tanja ; Hampe, Sarah ; Rottoli, Elsa ; Nadolni, Wiebke ; Perotti, Michela ; Meier, Melanie A. ; Hermanns, Constanze ; Geiger, Sheila ; Wennemuth, Gunther ; Recordati, Camilla ; Matsushita, Masayuki ; Muehlich, Susanne ; Proietti, Michele ; Chubanov, Vladimir ; Gudermann, Thomas ; Grassi, Fabio ; Zierler, Susanna

In: Nature communications, 2017, vol. 8, p. 1917

The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of ...

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...