Proietti, Michele; Cornacchione, Vanessa; Rezzonico Jost, Tanja; Romagnani, Andrea; Faliti, Caterina Elisa; Perruzza, Lisa; Rigoni, Rosita; Radaelli, Enrico; Caprioli, Flavio; Preziuso, Silvia; Brannetti, Barbara; Thelen, Marcus; McCoy, Kathleen; Slack, Emma; Traggiai, Elisabetta; Grassi, Fabio (2014). ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer's patches to promote host-microbiota mutualism. Immunity, 41(5), pp. 789-801. Cell Press 10.1016/j.immuni.2014.10.010
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Microbial colonization of the gut induces the development of gut-associated lymphoid tissue (GALT). The molecular mechanisms that regulate GALT function and result in gut-commensal homeostasis are poorly defined. T follicular helper (Tfh) cells in Peyer's patches (PPs) promote high-affinity IgA responses. Here we found that the ATP-gated ionotropic P2X7 receptor controls Tfh cell numbers in PPs. Lack of P2X7 in Tfh cells enhanced germinal center reactions and high-affinity IgA secretion and binding to commensals. The ensuing depletion of mucosal bacteria resulted in reduced systemic translocation of microbial components, lowering B1 cell stimulation and serum IgM concentrations. Mice lacking P2X7 had increased susceptibility to polymicrobial sepsis, which was rescued by Tfh cell depletion or administration of purified IgM. Thus, regulation of Tfh cells by P2X7 activity is important for mucosal colonization, which in turn results in IgM serum concentrations necessary to protect the host from bacteremia.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie |
UniBE Contributor: |
McCoy, Kathleen |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1074-7613 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Lilian Karin Smith-Wirth |
Date Deposited: |
17 Apr 2015 14:58 |
Last Modified: |
05 Dec 2022 14:45 |
Publisher DOI: |
10.1016/j.immuni.2014.10.010 |
PubMed ID: |
25464855 |
BORIS DOI: |
10.7892/boris.67004 |
URI: |
https://boris.unibe.ch/id/eprint/67004 |
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