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

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

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

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...