T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP
Open accessAbstract
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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Microbially derived ATP can modulate the host immune response through this pathway.
“Perruzza et al. recently demonstrated that microbially derived ATP can in fact modulate the host immune response through this pathway.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Perruzza et al., 2017
Monocolonization with a Shigella flexneri mutant unable to secrete ATP is associated with a significant increase in Tfh and germinal-center B cells and elevated bacteria-specific IgA in the intestine, compared with ATP-secreting wild-type S. flexneri.
“Monocolonization with a Shigella flexneri mutant unable to secrete ATP was associated with a significant increase in Tfh and germinal-center B cells, as well as elevated levels of bacteria-specific IgA in the intestine, compared to colonization with the ATP-secreting wild-type S. flexneri (Perruzza et al., 2017).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Perruzza et al., 2017
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- Authors
- Perruzza, L., Gargari, G., Proietti, M., Fosso, B., D’Erchia, A. M., Faliti, C. E., Rezzonico-Jost, T., Scribano, D., Mauri, L., Colombo, D., Pellegrini, G., Moregola, A., Mooser, C., Pesole, G., Nicoletti, M., Norata, G. D., Geuking, M. B., McCoy, K. D., Guglielmetti, S., & Grassi, F.
- Affiliations
- University of Bern (CH)
- University of Milan (IT)
- Institute for Research in Biomedicine (CH)
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- University of Chieti-Pescara (IT)
- University of Zurich (CH)
- Corresponding author
- Grassi, Fabio
- ORCID
- 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
- Norata, Giuseppe Danilo
- Geuking, Markus B.
- McCoy, Kathy D.
- Guglielmetti, Simone
- Grassi, Fabio
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 18
- Issue
- 11
- Pages
- 2566-2575
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5368345
- OpenAlex
- W2595845301
- Cited by
- 114
- References
- 26
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 17 · 2023: 9 · 2022: 14 · 2021: 9 · 2020: 18 · 2019: 17 · 2018: 8 · 2017: 3
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by-nc-nd)
- RERO DOC (Universität Bern) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion, cc-by-nc-nd)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eSpace (Curtin University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- European Research Council (281785, FP/2007-2013)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (12A09)
- Novartis Stiftung für Medizinisch-Biologische Forschung (20NA21_128841)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- T follicular helper cells, P2X7 receptor, extracellular ATP, gut microbiota, Peyer's patches, IgA, metabolic homeostasis, B cell help, commensal bacteria, intestinal mucosa
- MeSH terms
- Gastrointestinal Microbiome, Adenosine Triphosphate, Animals, Body Weight, Extracellular Space, Glucose, T-Lymphocytes, Helper-Inducer, Homeostasis, Immunoglobulin A, Intestine, Small, Mice, Inbred C57BL, Receptors, Purinergic P2X7
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