title: T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP.
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.
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3001 Bern 9, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Perruzza
authors.affiliation: Department of Food, Environmental, and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gargari
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Proietti
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fosso
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70126 Bari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Erchia
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3001 Bern 9, Switzerland.
authors.forename: Caterina Elisa
authors.initials: CE
authors.lastname: Faliti
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Rezzonico-Jost
authors.affiliation: Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D'Annunzio", 66100 Chieti, Italy; Departement of Public Health and Infectious Diseases, University "La Sapienza" of Rome, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Scribano
authors.affiliation: Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.affiliation: Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Colombo
authors.affiliation: Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellegrini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Moregola
authors.affiliation: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mooser
authors.affiliation: Institute of Biomembranes and Bioenergetics, National Research Council, 70126 Bari, Italy; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70126 Bari, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Pesole
authors.affiliation: Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D'Annunzio", 66100 Chieti, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Nicoletti
authors.affiliation: Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, 20133 Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6845, Australia.
authors.forename: Giuseppe Danilo
authors.initials: GD
authors.lastname: Norata
authors.affiliation: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 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, AB T2N 4N1, Canada.
authors.forename: Markus B
authors.initials: MB
authors.lastname: Geuking
authors.affiliation: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3010 Bern, Switzerland; Department of Physiology and Pharmacology and Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.affiliation: Department of Food, Environmental, and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Guglielmetti
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, 20129 Milan, Italy; Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi," 20122 Milan, Italy. Electronic address: fabio.grassi@irb.usi.ch.
authors.forename: Fabio
authors.initials: F
authors.lastname: Grassi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D005110:Extracellular Space / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007070:Immunoglobulin A / Q000378:metabolism; D007421:Intestine, Small / Q000382:microbiology; D008810:Mice, Inbred C57BL; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; C546469:P2rx7 protein, mouse; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D005947:Glucose
keywords: ATP; IgA; P2rx7; T follicular helper cells; metabolism; microbiota