MicroRNA-155-5p regulates the Th1/Th2 cytokines expression and the apoptosis of group 2 innate lymphiod cells via targeting TP53INP1 in allergic rhinitis
MicroRNA-155-5p regulates the Th1/Th2 cytokines expression and the apoptosis of group 2 innate lymphiod cells via targeting TP53INP1 in allergic rhinitis
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MicroRNA-155-5p通过靶向TP53INP1调节变应性鼻炎中Th1/Th2细胞因子的表达和第2组先天淋巴细胞的凋亡
DOI：
10.1016/j.intimp.2021.108317
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发表时间：
2021
影响因子：
5.6
通讯作者：
Yuehui Liu
中科院分区：
文献类型：
--
作者：
Yaqiong Zhu;Fan Ye;Yanpeng Fu;Xinhua Zhu;Yuehui Liu
第2组先天性淋巴样细胞（ILC 2）作为先天免疫的重要组成部分，在变应性鼻炎（AR）的发病中起着重要作用。我们先前证明了miR-155- 5 p和ILC 2在AR患者的鼻粘膜中过表达，但其潜在机制仍不清楚。目前的研究表明，miR-155- 5 p在AR患者ILC 2中高表达。miR-155- 5 p促进ILC 2s分泌Th 2型细胞因子，抑制ILC 2s分泌Th 1型细胞因子，抑制ILC 2s凋亡。同时，AR患者ILC 2中TP 53 INP 1表达较弱。双荧光素酶报告基因分析表明TP 53 INP 1是miR-155- 5 p的直接靶点，其表达与ILC 2中的miR-155- 5 p呈负相关。此外，TP 53 INP 1还能抑制ILC 2分泌Th 2型细胞因子，促进ILC 2分泌Th 1型细胞因子，促进ILC 2凋亡。值得注意的是，拯救实验证明TP 53 INP 1的过表达可以部分逆转miR-155- 5 p对ILC 2的作用。总而言之，这些发现表明miR-155- 5 p通过靶向TP 53 INP 1加剧了由ILC 2主导的AR的炎症反应，这可能有助于AR新型治疗药物的开发。
As a key component of innate immunity, group 2 innate lymphoid cells (ILC2s) play a key role in Allergic rhinitis (AR). We previously demonstrated that both miR-155-5p and ILC2s are overexpressed in the nasal mucosa of AR patients, but the underlying mechanism remains unclear. At present study, we revealed that miR-155-5p was highly expressed in ILC2s of AR patients. Moreover, miR-155-5p promoted the secretion of Th2 cytokines of ILC2s, while inhibited the secretion of Th1 cytokines and the apoptosis of ILC2s. Meanwhile, the TP53INP1 expression was poorly expressed in ILC2s of AR patients. A dual luciferase reporter assay demonstrated that TP53INP1 was a direct target of miR-155-5p, and its expression was inversely associated with miR-155-5p in ILC2s. Furthermore, TP53INP1 inhibited the secretion of Th2 cytokines of ILC2s, while promoted the secretion of Th1 cytokines and the apoptosis of ILC2s. Notably, rescue experiments demonstrated that overexpression of TP53INP1 could partially reverse the effect of miR-155-5p on ILC2s. Taken together, these findings suggested that miR-155-5p aggravated the inflammatory response of AR dominated by ILC2s via targeting TP53INP1, which may aid in the development of novel therapeutic agents for AR.