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

Immunity. 2014 Nov 20;41(5):789-801. doi: 10.1016/j.immuni.2014.10.010. Epub 2014 Nov 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • B-Lymphocytes / immunology
  • Bacteremia / immunology
  • Genetic Predisposition to Disease
  • Germinal Center / immunology
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin M / blood
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota / immunology
  • Peyer's Patches / cytology
  • Peyer's Patches / immunology*
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / immunology*
  • Sepsis / immunology
  • Sepsis / microbiology
  • Symbiosis / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Immunoglobulin A
  • Immunoglobulin M
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate

Associated data

  • SRA/SRP049293