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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

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...