Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.

Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.
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DOI:
10.1016/j.immuni.2012.11.001
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发表时间:
2012-12-14
期刊:
影响因子:
32.4
通讯作者:
Becher B
Becher B
中科院分区:
医学1区
文献类型:
--
作者:
Greter M;Lelios I;Pelczar P;Hoeffel G;Price J;Leboeuf M;Kündig TM;Frei K;Ginhoux F;Merad M;Becher B

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集落刺激因子 1 (Csf-1) 受体及其配体 Csf-1 控制巨噬细胞的发育、维持和功能。朗格汉斯细胞 (LC) 和小胶质细胞的发育高度依赖于 Csf-1 受体信号传导,但独立于 Csf-1。在这里,我们表明,在小鼠和人类中,白细胞介素 34 (IL-34)(Csf-1 受体的替代配体)是由表皮中的角质形成细胞和大脑中的神经元产生的。缺乏IL-34的小鼠表现出LC显着减少和小胶质细胞减少,而单核细胞、真皮和淋巴组织巨噬细胞和DC不受影响。我们确定 IL-34 是胚胎发生过程中 LC 发育及其在成人皮肤中稳态的非冗余细胞因子。尽管炎症诱导的 LC 重新增殖似乎依赖于 Csf-1,但一旦炎症得到解决,LC 的存活率又依赖于 IL-34。相比之下,小胶质细胞及其卵黄囊前体的发育独立于 IL-34,但在成人大脑中依赖它来维持。
Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain. Mice lacking IL-34 displayed a marked reduction of LCs and a decrease of microglia, whereas monocytes, dermal, and lymphoid tissue macrophages and DCs were unaffected. We identified IL-34 as a nonredundant cytokine for the development of LCs during embryo-genesis as well as for their homeostasis in the adult skin. Whereas inflammation-induced repopulation of LCs appears to be dependent on Csf-1, once inflammation is resolved, LC survival is again IL-34-dependent. In contrast, microglia and their yolk sac precursors develop independently of IL-34 but rely on it for their maintenance in the adult brain.
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影响因子: 11.1
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