Prostaglandin E₂ constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.
Prostaglandin E₂ constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.
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DOI：
10.1126/science.aad9903
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发表时间：
2016-03-18
期刊：
影响因子：
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通讯作者：
Yao C
中科院分区：
文献类型：
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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
由促炎分子大量释放到循环系统中引起的全身性炎症是严重疾病的主要风险因素，但其控制的确切机制尚不完全清楚。我们观察到前列腺素E2（PGE 2）通过其受体EP 4在人类全身性炎症性疾病中下调。PGE2合成减少的小鼠发生与肠道细菌移位相关的全身性炎症，这可以通过用EP 4激动剂治疗来预防。从机制上讲，我们证明PGE2-EP4信号直接作用于3型先天淋巴细胞（ILC），促进其体内平衡并驱动其产生白细胞介素-22（IL-22）。ILC/IL-22轴的破坏损害了PGE2介导的对全身性炎症的抑制。因此，PGE2-EP4信号通过ILC/IL-22轴依赖性保护肠道屏障功能障碍来抑制全身性炎症。
Systemic inflammation, resulting from massive release of pro-inflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are incompletely understood. We observed that prostaglandin E2 (PGE2) through its receptor EP4 is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treating with EP4 agonists. Mechanistically, we demonstrate that PGE2–EP4 signaling directly acts on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC/IL-22 axis impairs PGE2–mediated inhibition of systemic inflammation. Hence, PGE2–EP4 signaling inhibits systemic inflammation through ILC/IL-22 axis–dependent protection of gut barrier dysfunction.