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T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP

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Authors
Perruzza, L.
Gargari, G.
Proietti, M.
Fosso, B.
D'Erchia, A.
Faliti, C.
Rezzonico-Jost, T.
Scribano, D.
Mauri, L.
Colombo, D.
Pellegrini, G.
Moregola, A.
Mooser, C.
Pesole, G.
Nicoletti, M.
Norata, Giuseppe
Geuking, M.
McCoy, K.
Guglielmetti, S.
Grassi, F.
Date
2017
Type
Journal Article

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Perruzza, L. and Gargari, G. and Proietti, M. and Fosso, B. and D'Erchia, A. and Faliti, C. and Rezzonico-Jost, T. et al. 2017. T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP. Cell Reports. 18 (11): pp. 2566-2575.
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Cell Reports
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School of Biomedical Sciences
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Abstract

© 2017 The Authors 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.