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MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2017-12-04 , DOI: 10.1084/jem.20170545
Priti B. Singh 1, 2 , Heather H. Pua 2, 3 , Hannah C. Happ 1, 2 , Christoph Schneider 4 , Jakob von Moltke 4 , Richard M. Locksley 2, 4, 5 , Dirk Baumjohann 6 , K. Mark Ansel 1, 2
Affiliation  

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92–deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses.



中文翻译:

MicroRNA调节2型先天淋巴样细胞稳态和变态反应性炎症的功能

MicroRNA(miRNA)通过多种细胞中多个靶基因的协调调控,对免疫力产生强大影响。2型先天淋巴样细胞(ILC2s)是变态反应性炎症的组织前哨介质。我们确定了ILC2稳态和免疫功能中miRNA的生理要求,并比较了静息和激活的ILC2s和2型T辅助细胞(T H2)细胞。暴露于天然变应原木瓜蛋白酶后,ILC2s中选择性缺乏miR-17〜92簇的小鼠表现出减少的肺部炎症。此外,miR-17〜92缺失的ILC2在体外对IL-33和胸腺基质淋巴细胞生成素的生长和细胞因子表达有缺陷。miR-17〜92簇成员miR-19a促进IL-13和IL-5的产生,并抑制包括SOCS1和A20在内的几种靶标的表达,这是限制IL-13和IL-5产生的信号抑制剂。这些发现将miRNA确立为ILC2生物学的重要调控因子,揭示了重叠但不完全相同的miRNA调控的ILC2s和T H 2细胞中的基因表达网络,并增强了靶向miR-19减轻病原性变态反应的治疗潜力。

更新日期:2017-11-30
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