ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer's patches to promote host-microbiota mutualism.

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:

06 Nov 2015 09:38

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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