IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury

IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury
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IL-25 诱导先天淋巴细胞和多能祖细胞 2 型,减少肾缺血/再灌注损伤。

DOI:
10.1681/asn.2014050479
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发表时间:
2015-09-01
影响因子:
13.6
通讯作者:
Cao, Qi
Cao, Qi
中科院分区:
医学1区
文献类型:
--
作者:
Huang, Qingsong;Niu, Zhiguo;Cao, Qi

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IL-25是一种重要的免疫调节剂,在哮喘、肠道感染和自身免疫性疾病中可以促进Th2免疫反应依赖性免疫、炎症和组织修复。在这项研究中,我们检测了IL-25在肾缺血/再灌注损伤(IRI)中的作用。用IL-25治疗IRI小鼠可显著改善肾功能,减轻肾损伤。此外,IL-25处理提高了血清和肾脏中IL-4、IL-5和IL-13的水平,促进了肾脏中替代活化(M2)巨噬细胞的诱导。值得注意的是,IL-25治疗还增加了肾脏中2型先天淋巴样细胞(ILC2s)和2型多能祖细胞(MPP(2型))的频率。il -25响应的ILC2和MPP(2型)细胞产生更多的Th2细胞因子,这些细胞因子与体外诱导M2巨噬细胞和抑制经典活化(M1)巨噬细胞有关。最后,ILC2s或MPP(2型)细胞过继性转移不仅可以减轻IRI小鼠的肾功能和组织学损伤,还可以诱导肾中M2巨噬细胞的形成。总之,我们的数据确定了il -25诱导的ILC2和MPP(2型)细胞调节肾脏巨噬细胞表型和预防肾脏IRI的机制。
IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPP(type2)) cells in kidney. IL-25-responsive ILC2 and MPP(type2) cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPP(type2) cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPP(type2) cells regulate macrophage phenotype in kidney and prevent renal IRI.