T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP

Cell Rep. 2017 Mar 14;18(11):2566-2575. doi: 10.1016/j.celrep.2017.02.061.

Abstract

The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help.

Keywords: ATP; IgA; P2rx7; T follicular helper cells; metabolism; microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Body Weight
  • Extracellular Space / metabolism*
  • Gastrointestinal Microbiome / immunology*
  • Glucose / metabolism
  • Homeostasis*
  • Immunoglobulin A / metabolism
  • Intestine, Small / microbiology
  • Mice, Inbred C57BL
  • Receptors, Purinergic P2X7 / deficiency
  • Receptors, Purinergic P2X7 / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Immunoglobulin A
  • P2rx7 protein, mouse
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • Glucose