TY - JOUR
T1 - ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in peyer's patches to promote host-microbiota mutualism
AU - Proietti, Michele
AU - Cornacchione, Vanessa
AU - RezzonicoJost, Tanja
AU - Romagnani, Andrea
AU - Faliti, Caterina Elisa
AU - Perruzza, Lisa
AU - Rigoni, Rosita
AU - Radaelli, Enrico
AU - Caprioli, Flavio
AU - Preziuso, Silvia
AU - Brannetti, Barbara
AU - Thelen, Marcus
AU - McCoy, Kathy D.
AU - Slack, Emma
AU - Traggiai, Elisabetta
AU - Grassi, Fabio
PY - 2014/11/20
Y1 - 2014/11/20
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84912086043&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.10.010
DO - 10.1016/j.immuni.2014.10.010
M3 - Article
C2 - 25464855
AN - SCOPUS:84912086043
VL - 41
SP - 789
EP - 801
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 5
ER -