Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
复制标题
神经 - 免疫相互作用驱动肠道巨噬细胞中的组织编程。
DOI：
10.1016/j.cell.2015.12.023
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发表时间：
2016-01-28
期刊：
影响因子：
64.5
通讯作者：
Mucida D
中科院分区：
文献类型：
--
作者：
Gabanyi I;Muller PA;Feighery L;Oliveira TY;Costa-Pinto FA;Mucida D
适当适应环境扰动对于组织稳态至关重要。在肠道中，免疫细胞可以感受到不同的环境信号，它们必须平衡对微生物的抵抗力和耐受性，避免过度的组织损伤。通过应用成像和转录分析工具，我们询问了肠道中不同的微环境如何调节驻留的巨噬细胞。我们发现，巨噬细胞表现出高度的基因表达专业化依赖于他们接近肠腔。固有层巨噬细胞（LpMs）优先表达的促炎表型相比，肌层巨噬细胞（ESTA），显示组织保护表型。在管腔细菌感染后，Escherichia coli进一步增强组织保护程序，这归因于神经支配肠肌层的外源性交感神经元的快速激活和去甲肾上腺素信号传导至Escherichia coli上的β2肾上腺素能受体。我们的研究结果揭示了独特的组织内巨噬细胞专业化，并确定肠神经元和巨噬细胞之间的神经免疫通讯，诱导快速的组织保护反应，远端扰动。
Proper adaptation to environmental perturbations is essential for tissue homeostasis. In the intestine, diverse environmental cues can be sensed by immune cells, which must balance resistance to microorganisms with tolerance, avoiding excess tissue damage. By applying imaging and transcriptional profiling tools, we interrogated how distinct microenvironments in the gut regulate resident macrophages. We discovered that macrophages exhibit a high degree of gene-expression specialization dependent on their proximity to the gut lumen. Lamina propria macrophages (LpMs) preferentially expressed a pro-inflammatory phenotype when compared to muscularis macrophages (MMs), which displayed a tissue-protective phenotype. Upon luminal bacterial infection, MMs further enhanced tissue-protective programs, and this was attributed to swift activation of extrinsic sympathetic neurons innervating the gut muscularis and norepinephrine signaling to β2 adrenergic receptors on MMs. Our results reveal unique intra-tissue macrophage specialization and identify neuro-immune communication between enteric neurons and macrophages that induces rapid tissue-protective responses to distal perturbations.