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Publication : Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A(2B)AR signaling in intestinal epithelial cells.

First Author  El-Naccache DW Year  2022
Journal  Cell Rep Volume  40
Issue  5 Pages  111150
PubMed ID  35926464 Mgi Jnum  J:336691
Mgi Id  MGI:7329670 Doi  10.1016/j.celrep.2022.111150
Citation  El-Naccache DW, et al. (2022) Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells. Cell Rep 40(5):111150
abstractText  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.
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