Purine metabolism controls innate lymphoid cell function and protects against intestinal injury.
Purine metabolism controls innate lymphoid cell function and protects against intestinal injury.
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DOI：
10.1111/imcb.12167
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发表时间：
2018-11
影响因子：
4
通讯作者：
Yao C
中科院分区：
文献类型：
--
作者：
Crittenden S;Cheyne A;Adams A;Forster T;Robb CT;Felton J;Ho GT;Ruckerl D;Rossi AG;Anderton SM;Ghazal P;Satsangi J;Howie SE;Yao C
炎症性肠病（IBD）是一种慢性炎症性肠道疾病，患病率不断上升，但有效的治疗方法有限。嘌呤代谢途径参与包括IBD在内的多种炎症过程。然而，嘌呤代谢调节IBD的机制仍有待建立。在这里，我们发现参与嘌呤代谢途径的基因在活动性溃疡性结肠炎（UC）患者的粘膜表达发生改变，这与第3组先天淋巴样细胞(ILC3) -白细胞介素（IL）‐22途径的基因表达特征升高有关。在小鼠实验中，胞外腺苷5 ' -三磷酸（eATP）水解成腺苷代谢嘌呤的关键酶——外核苷酶（ntpases）被阻断会加重葡聚糖硫酸钠诱导的肠道损伤。这种结肠炎的恶化与结肠产生IL - 22的ILC3s的减少有关，ILC3s对肠道炎症提供必要的保护，并由外源性IL - 22拯救。从机制上讲，IL - 22产生的ILC3s激活是由eATP和腺苷相互介导的。这些研究结果表明，ntpase介导的eATP和腺苷之间的平衡调节了ILC3细胞的功能，以保护肠道免受损伤，并为靶向嘌呤- ILC3轴治疗IBD提供了潜在的治疗策略。
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 ILC3 cell function to provide protection against intestinal injury and suggest potential therapeutic strategies for treating IBD by targeting the purine–ILC3 axis.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
DOI：
10.1126/science.aad9903
发表时间：
2016-03-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Duffin R;O'Connor RA;Crittenden S;Forster T;Yu C;Zheng X;Smyth D;Robb CT;Rossi F;Skouras C;Tang S;Richards J;Pellicoro A;Weller RB;Breyer RM;Mole DJ;Iredale JP;Anderton SM;Narumiya S;Maizels RM;Ghazal P;Howie SE;Rossi AG;Yao C
通讯作者：
Yao C
影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
炎症过程中的核苷酸信号传导。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten