51. T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP
- Author
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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, 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, and Grassi, Fabio
- Abstract
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 microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help.