Adenosine Metabolized from Extracellular ATP Promotes Type 2 Immunity Through Triggering AAR Signaling in Intestinal Epithelial Cells

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Aug 4

PMID 35926464

Authors

Darine W El-Naccache

Fei Chen

Mark J Palma

Alexander Lemenze

Matthew A Fischer

Wenhui Wu

Pankaj K Mishra

Holger K Eltzschig

Simon C Robson

Francesco Di Virgilio

George S Yap

Karen L Edelblum

Gyorgy Hasko

William C Gause

Affiliations

Soon will be listed here.

Abstract

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A adenosine receptor (AAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC AAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

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