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MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells.
Immunity ( IF 32.4 ) Pub Date : 2019-08-08 , DOI: 10.1016/j.immuni.2019.06.016
Melissa M Berrien-Elliott 1 , Yaping Sun 2 , Carly Neal 1 , Aaron Ireland 1 , Maria C Trissal 1 , Ryan P Sullivan 1 , Julia A Wagner 1 , Jeffrey W Leong 1 , Pamela Wong 1 , Annelise Y Mah-Som 3 , Terrence N Wong 1 , Timothy Schappe 1 , Catherine R Keppel 1 , Victor S Cortez 4 , Efstathios G Stamatiades 5 , Ming O Li 5 , Marco Colonna 4 , Daniel C Link 1 , Anthony R French 3 , Megan A Cooper 3 , Wei-Le Wang 6 , Mark P Boldin 6 , Pavan Reddy 2 , Todd A Fehniger 1
Affiliation  

Natural killer (NK) cells are cytotoxic type 1 innate lymphoid cells (ILCs) that defend against viruses and mediate anti-tumor responses, yet mechanisms controlling their development and function remain incompletely understood. We hypothesized that the abundantly expressed microRNA-142 (miR-142) is a critical regulator of type 1 ILC biology. Interleukin-15 (IL-15) signaling induced miR-142 expression, whereas global and ILC-specific miR-142-deficient mice exhibited a cell-intrinsic loss of NK cells. Death of NK cells resulted from diminished IL-15 receptor signaling within miR-142-deficient mice, likely via reduced suppressor of cytokine signaling-1 (Socs1) regulation by miR-142-5p. ILCs persisting in Mir142-/- mice demonstrated increased expression of the miR-142-3p target αV integrin, which supported their survival. Global miR-142-deficient mice exhibited an expansion of ILC1-like cells concurrent with increased transforming growth factor-β (TGF-β) signaling. Further, miR-142-deficient mice had reduced NK-cell-dependent function and increased susceptibility to murine cytomegalovirus (MCMV) infection. Thus, miR-142 critically integrates environmental cues for proper type 1 ILC homeostasis and defense against viral infection.

中文翻译:

MicroRNA-142对于1型先天淋巴样细胞的稳态和功能至关重要。

天然杀伤(NK)细胞是可抵抗病毒并介导抗肿瘤反应的细胞毒性1型先天淋巴样细胞(ILC),但控制其发育和功能的机制仍不完全清楚。我们假设,大量表达的microRNA-142(miR-142)是1型ILC生物学的关键调节因子。白介素15(IL-15)信号传导诱导miR-142表达,而整体和ILC特异性miR-142缺陷小鼠表现出NK细胞的细胞内在丧失。NK细胞的死亡是由于miR-142缺陷型小鼠中IL-15受体信号减弱导致的,这可能是由于miR-142-5p对细胞因子信号传导1(Socs1)调节的抑制因子降低所致。在Mir142-/-小鼠中持续存在的ILCs证明了miR-142-3p靶标αV整联蛋白的表达增加,这支持了它们的生存。全球性miR-142缺陷小鼠表现出ILC1样细胞的扩张,同时转化生长因子-β(TGF-β)信号传导增加。此外,miR-142缺陷小鼠的NK细胞依赖性功能降低,对鼠巨细胞病毒(MCMV)感染的敏感性增加。因此,miR-142至关重要地整合了环境线索,以实现正确的1型ILC稳态和防御病毒感染。
更新日期:2019-08-09
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