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Purine metabolism controls innate lymphoid cell function and protects against intestinal injury
Author(s) -
Crittenden Siobhan,
Cheyne Ashleigh,
Adams Alexander,
Forster Thorsten,
Robb Calum T,
Felton Jennifer,
Ho GwoTzer,
Ruckerl Dominik,
Rossi Adriano G,
Anderton Stephen M,
Ghazal Peter,
Satsangi Jack,
Howie Sarah E,
Yao Chengcan
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12167
Subject(s) - adenosine , purine metabolism , purine , inflammatory bowel disease , colitis , inflammation , immunology , ulcerative colitis , biology , chemistry , medicine , enzyme , biochemistry , disease
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 ( ILC 3)–interleukin ( IL )‐22 pathway. In mice, blockade of ectonucleotidases ( NTPD ases), 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 ILC 3s, which afford essential protection against intestinal inflammation, and is rescued by exogenous IL ‐22. Mechanistically, activation of ILC 3s for IL ‐22 production is reciprocally mediated by eATP and adenosine. These findings reveal that the NTPD ase‐mediated balance between eATP and adenosine regulates ILC 3 cell function to provide protection against intestinal injury and suggest potential therapeutic strategies for treating IBD by targeting the purine– ILC 3 axis.