The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection
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DOI：
10.1038/ni.1920
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发表时间：
2010-10-01
影响因子：
30.5
通讯作者：
Akira, Shizuo
中科院分区：
文献类型：
--
作者：
Satoh, Takashi;Takeuchi, Osamu;Akira, Shizuo
巨噬细胞向M1或M2细胞的极化对于分别针对细菌和蠕虫感染的安装反应是重要的。Jumonji domain containing-3（Jmjd 3）是一种组蛋白3Lys 27（H3 K27）去甲基化酶，与巨噬细胞的活化有关。在这里，我们表明，Jmjd 3是必不可少的M2巨噬细胞极化蠕虫感染和几丁质的反应，虽然Jmjd 3是M1的反应。此外，Jmjd 3（也称为Kdm 6 b）对于适当的骨髓巨噬细胞分化是必不可少的，并且该功能取决于Jmjd 3的脱甲基酶活性。Jmjd 3缺陷只在有限数量的基因中影响H3 K27的三甲基化。其中，我们确定Irf 4编码一个关键的转录因子，控制M2巨噬细胞极化。总的来说，这些结果表明，Jmjd 3介导的H3 K27去甲基化对于调节M2巨噬细胞发育至关重要，从而导致抗蠕虫宿主应答。
Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infections, respectively. Jumonji domain containing-3 (Jmjd3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in the activation of macrophages. Here we show that Jmjd3 is essential for M2 macrophage polarization in response to helminth infection and chitin, though Jmjd3 is dispensable for M1 responses. Furthermore, Jmjd3 (also known as Kdm6b) is essential for proper bone marrow macrophage differentiation, and this function depends on demethylase activity of Jmjd3. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited number of genes. Among them, we identified Irf4 as encoding a key transcription factor that controls M2 macrophage polarization. Collectively, these results show that Jmjd3-mediated H3K27 demethylation is crucial for regulating M2 macrophage development leading to anti-helminth host responses.