Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells.

Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells.
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白介素-9产生2型先天淋巴样细胞炎症的分辨率。

DOI:
10.1038/nm.4373
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发表时间:
2017-08
期刊:
影响因子:
82.9
通讯作者:
Ramming A
Ramming A
中科院分区:
医学1区
文献类型:
--
作者:
Rauber S;Luber M;Weber S;Maul L;Soare A;Wohlfahrt T;Lin NY;Dietel K;Bozec A;Herrmann M;Kaplan MH;Weigmann B;Zaiss MM;Fearon U;Veale DJ;Cañete JD;Distler O;Rivellese F;Pitzalis C;Neurath MF;McKenzie ANJ;Wirtz S;Schett G;Distler JHW;Ramming A

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炎症性疾病,如关节炎,是一种不能自行消退的慢性疾病。虽然触发关节炎的细胞因子和细胞通路是明确的,但那些负责解决炎症的细胞因子和细胞通路尚未完全确定。在这里,我们发现产生il -9的2型先天淋巴样细胞(ILC2s)是协调慢性炎症解决的分子和细胞途径。在小鼠中,IL-9的缺失会损害ILC2的增殖、调节性T细胞(Treg)的激活,并导致慢性关节炎伴软骨过度破坏和骨质流失。相比之下,用IL-9治疗可促进ilc2依赖性Treg活化,并有效诱导炎症消退和骨骼保护。缓解期的类风湿关节炎患者在关节和循环中表现出大量的IL-9+ ILC2s。因此,促进il -9介导的ILC2激活可能提供一种新的治疗方法,诱导炎症的消退,而不是抑制炎症反应。
Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified IL-9-producing type 2 innate lymphoid cells (ILC2s) as a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation, activation of regulatory T cells (Treg) and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent Treg activation and effectively induced resolution of inflammation and protection of bone. Rheumatoid arthritis patients in remission demonstrated high numbers of IL-9+ ILC2s in the joints and in the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.
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