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
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    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.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318969
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