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摘要 : Henrique Veiga-Fernandes及同事发现,肠胶质细胞响应于来自微生物群的提示所产生的神经营养因子,有助于肠道中白介素-22的生成和 “Group 3” 先天淋巴细胞的调控。

 Henrique Veiga-Fernandes及同事发现,肠胶质细胞响应于来自微生物群的提示所产生的神经营养因子,有助于肠道中白介素-22的生成和 “Group 3” 先天淋巴细胞的调控。在一个肠炎模型中,这一通道的破坏导致鼠类柠檬酸杆菌 (Citrobacter rodentium)的清除受损和上皮完整性的缺陷。


Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence


Group 3 innate lymphoid cells (ILC3) are major regulators of inflammation and infection at mucosal barriers1. ILC3 development is thought to be programmed1, but how ILC3 perceive, integrate and respond to local environmental signals remains unclear. Here we show that ILC3 in mice sense their environment and control gut defence as part of a glial–ILC3–epithelial cell unit orchestrated by neurotrophic factors. We found that enteric ILC3 express the neuroregulatory receptor RET. ILC3-autonomous Ret ablation led to decreased innate interleukin-22 (IL-22), impaired epithelial reactivity, dysbiosis and increased susceptibility to bowel inflammation and infection. Neurotrophic factors directly controlled innate Il22 downstream of the p38 MAPK/ERK-AKT cascade and STAT3 activation. Notably, ILC3 were adjacent to neurotrophic-factor-expressing glial cells that exhibited stellate-shaped projections into ILC3 aggregates. Glial cells sensed microenvironmental cues in a MYD88-dependent manner to control neurotrophic factors and innate IL-22. Accordingly, glial-intrinsic Myd88 deletion led to impaired production of ILC3-derived IL-22 and a pronounced propensity towards gut inflammation and infection. Our work sheds light on a novel multi-tissue defence unit, revealing that glial cells are central hubs of neuron and innate immune regulation by neurotrophic factor signals.

来源: Nature 浏览次数:1


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