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

doi:10.1016/j.celrep.2017.02.061

Back

Journal article

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

Perruzza, Lisa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
Gargari, Giorgio Department of Food, Environmental, and Nutritional Sciences (DeFENS), Universita` degli Studi di Milano, Milan, Italy
Proietti, Michele Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Fosso, Bruno Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy
D'Erchia, Anna Maria Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
Faliti, Caterina Elisa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
Rezzonico-Jost, Tanja Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Scribano, Daniela Department of Medical and Oral Sciences and Biotechnologies, University ‘‘Gabriele D’Annunzio’’, Chieti, Italy - Departement of Public Health and Infectious Diseases, University ‘‘La Sapienza’’ of Rome, Rome, Italy
Mauri, Laura Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita` degli Studi di Milano, Milan, Italy
Colombo, Diego Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita` degli Studi di Milano, Milan, Italy
Pellegrini, Giovanni Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
Moregola, Annalisa Department of Pharmacological and Biomolecular Sciences (DiSFeB), Universita` degli Studi di Milano, Milan, Italy
Mooser, Catherine Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, Bern, Switzerland
Pesole, Graziano Institute of Biomembranes and Bioenergetics, National Research Council, Bari, Italy - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
Nicoletti, Mauro Department of Medical and Oral Sciences and Biotechnologies, University ‘‘Gabriele D’Annunzio’’, Chieti, Italy
Norata, Giuseppe Danilo Department of Pharmacological and Biomolecular Sciences (DiSFeB), Universita` degli Studi di Milano, Milan, Italy - School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia
Geuking, Markus B. Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, Bern, Switzerland - Department of Microbiology, Immunology and Infectious Diseases and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada
McCoy, Kathy D. Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, Bern, Switzerland
Guglielmetti, Simone Department of Food, Environmental, and Nutritional Sciences (DeFENS), Universita` degli Studi di Milano, Milan, Italy
Grassi, Fabio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universita` degli Studi di Milano, Milan, Italy - Istituto Nazionale Genetica Molecolare ‘‘Romeo ed Enrica Invernizzi,’’ Milan, Italy

14.03.2017

Published in:

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

English 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.

Language