Cell Reports
(Mar 2017)
T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP
Lisa Perruzza,
Giorgio Gargari,
Michele Proietti,
Bruno Fosso,
Anna Maria D’Erchia,
Caterina Elisa Faliti,
Tanja Rezzonico-Jost,
Daniela Scribano,
Laura Mauri,
Diego Colombo,
Giovanni Pellegrini,
Annalisa Moregola,
Catherine Mooser,
Graziano Pesole,
Mauro Nicoletti,
Giuseppe Danilo Norata,
Markus B. Geuking,
Kathy D. McCoy,
Simone Guglielmetti,
Fabio Grassi
Affiliations
Lisa Perruzza
Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
Giorgio Gargari
Department of Food, Environmental, and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133 Milan, Italy
Michele Proietti
Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
Bruno Fosso
Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy
Anna Maria D’Erchia
Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy
Caterina Elisa Faliti
Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
Tanja Rezzonico-Jost
Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
Daniela Scribano
Department of Medical and Oral Sciences and Biotechnologies, University “Gabriele D'Annunzio”, 66100 Chieti, Italy
Laura Mauri
Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milan, Italy
Diego Colombo
Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milan, Italy
Giovanni Pellegrini
Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Annalisa Moregola
Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, 20133 Milan, Italy
Catherine Mooser
Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland
Graziano Pesole
Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy
Mauro Nicoletti
Department of Medical and Oral Sciences and Biotechnologies, University “Gabriele D'Annunzio”, 66100 Chieti, Italy
Giuseppe Danilo Norata
Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, 20133 Milan, Italy
Markus B. Geuking
Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland
Kathy D. McCoy
Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland
Simone Guglielmetti
Department of Food, Environmental, and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133 Milan, Italy
Fabio Grassi
Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
DOI
https://doi.org/10.1016/j.celrep.2017.02.061
Journal volume & issue
Vol. 18,
no. 11
pp.
2566
– 2575
Abstract
Read online
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.
Keywords
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