Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

Immunology and Cell Biology
Siobhan CrittendenChengcan Yao

Abstract

Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)-interleukin (IL)-22 pathway. In mice, blockade of ectonucleotidases (NTPDases), critical enzymes for purine metabolism by hydrolysis of extracellular adenosine 5'-triphosphate (eATP) into adenosine, exacerbates dextran-sulfate sodium-induced intestinal injury. This exacerbation of colitis is associated with reduction of colonic IL-22-producing ILC3s, which afford essential protection against intestinal inflammation, and is rescued by exogenous IL-22. Mechanistically, activation of ILC3s for IL-22 production is reciprocally mediated by eATP and adenosine. These findings reveal that the NTPDase-mediated balance between eATP and adenosine regulates IL...Continue Reading

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Citations

Oct 9, 2018·Immunological Reviews·Ann M JosephGregory F Sonnenberg
Dec 18, 2020·Frontiers in Immunology·Ali AminiPaul Klenerman
Feb 23, 2021·Frontiers in Pharmacology·Anna Lisa GiulianiFrancesco Di Virgilio
Apr 22, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clarissa Branco HaasGyörgy Haskó

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Datasets Mentioned

BETA
GSE59071
GSE11223

Methods Mentioned

BETA
biopsies
deamination
biopsy
flow cytometry
FCS

Software Mentioned

Prism
FlowJo
GraphPad
Photoshop

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