Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells
Darine W. El-Naccache, Fei Chen, Mark Palma, Alexander Lemenze, Matthew Fischer, Wenhui Wu, Pankaj Kumar Mishra, Holger K. Eltzschig, Simon C. Robson, Francesco Di Virgilio, George Yap, Karen L. Edelblum, György Haskó, William C. Gause
Abstract
AR 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.