Role of ATP gated ionotropic P2X7 receptor in regulating adaptive mucosal immunity, host-microbiota mutualism

• Research unit: COST
• Project number: C16.0016

Key words (English)

Ion channels; immune cells; cancer; auto-immune and inflammatory diseases; therapeutic approaches

Research programs (English)

COST-Action BM1406 - IONCHAN-IMMUNRESPON: ION CHANnels and IMMUNe RESPONse Toward a global understanding of immune cell physiology And for new therapeutic approaches

Short description (English)

Intestinal IgA in response to microbial stimulation is produced in the gut associated lymphoid tissue. T follicular helper (Tfh) cells in Peyer’s patches (PPs) of the small intestine promote B cells expansion, class switch recombination and affinity IgA maturation. Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger, which activates purinergic receptors in the plasma membrane termed P2 receptors. The P2X7 receptor subtype is an ATP-gated nonselective cationic channel expressed in a variety of cell types. In T cells protracted receptor stimulation leads to cell death. P2X7 regulates Tfh cells abundance in PPs. Lack of P2X7 in Tfh cells enhanced the germinal centre reaction, high affinity IgA secretion and binding to commensals. P2rx7 -/- mice display features reminiscent of metabolic syndrome. Analysis of the gut microbiota with genus specific probes revealed a 3-fold increase in the ratio between Firmicutes and Bacteroides. Within this project we will address the role of Tfh cells expansion and altered gut microbiota composition in the establishment of p2rx7 -/- mice metabolic phenotype. We will combine functional, biochemical and bioenergetic approaches to characterize the metabolic reprogramming underlying the enhanced functional potential of Tfh cells lacking P2X7. Altogether this project will allow drawing a picture on the role of P2X7 in regulating mucosal adaptive immune response, host-microbiota mutualism and systemic metabolism

Partners and International Organizations (English)

AT; BA; HR; CZ; DK; EE; FR; MK; DE; EL; HU; IL; IT; LV; LU; NO; PL; PT; RS; SI; ES, SE; TR; UK; IE

Abstract (English)

See short description

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C16.0016