Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells

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, György Haskó, William C. Gause

Research output: Contribution to journalArticlepeer-review

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 A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR 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.

Original languageEnglish (US)
Article number111150
JournalCell Reports
Volume40
Issue number5
DOIs
StatePublished - Aug 2 2022

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Keywords

  • CP: Immunology
  • CP: Molecular biology

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