Proietti, M, Cornacchione, V, RezzonicoJost, T, Romagnani, A, Faliti, CE, Perruzza, L, Rigoni, R, Radaelli, E, Caprioli, F, Preziuso, S, Brannetti, B, Thelen, M, McCoy, KD, Slack, E, Traggiai, E and Grassi, F (2014) ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in peyer's patches to promote host-microbiota mutualism. Immunity. pp. 789-801.

Abstract

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:	Article
Additional Information:	NIBR author: Brannetti, B institute: NIBR contributor address: (Proietti, Cornacchione, RezzonicoJost, Romagnani, Faliti, Perruzza, Rigoni, Thelen, Grassi) Institute for Research in Biomedicine, Via Vincenzo Vela 6, Bellinzona 6500, Switzerland (Cornacchione, Brannetti, Traggiai) Novartis Institute for Biomedical Research, Fabrickstrasse 2, Basel 4002, Switzerland (Romagnani, Faliti, Perruzza) Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, Bern 3012, Switzerland (Radaelli) Fondazione Filarete, Viale Ortles 22/4, Milan 20139, Italy (Caprioli) Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, Milan 20122, Italy (Caprioli) Unit of Gastroenterology 2, Fondazione IRCCS Ca' Granda, Ospedale Policlinico di Milano, Via Francesco Sforza 35, Milan 20122, Italy (Preziuso) Department of Veterinary Medical Sciences, University of Camerino, Via Circonvallazione 93/95, Matelica 62024, Italy (McCoy) Maurice Muller Laboratories, Universitatsklinik fur Viszerale Chirurgie und Medizin (UVCM), University of Bern, Murtenstrasse 35, Bern 3010, Switzerland (Slack) Institute of Microbiology, ETH Zurich, HCI F 413 Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland (Grassi) Department of Medical Biotechnology and Translational Medicine, University of Milan, Via G.B. Viotti 3/5, Milan 20133, Italy
Date Deposited:	13 Oct 2015 13:11
Last Modified:	13 Oct 2015 13:11
URI:	https://oak.novartis.com/id/eprint/24920