2023年8月18日，来自美国基因泰克公司Frederic J. de Sauvage研究组在学术期刊《细胞-干细胞》发表了标题为”Adrenergic nerves regulate intestinal regeneration through IL-22 signaling from type 3 innate lymphoid cells.“的研究成果。发现肾上腺素能神经通过3型先天淋巴细胞（ILC3s）分泌的IL-22信号传导调节肠道再生。
肠道非常容易受到影响，并在癌症治疗过程中受到改变DNA的试剂(如放疗和化疗）造成的恶劣条件的影响。例如，许多胃肠道肿瘤患者接受放疗，这种治疗往往也会损害健康肠道，影响它的再生能力。因此，了解肠道上皮的再生是如何发生的非常重要。
据介绍，肠上皮细胞具有较高的内在周转率，上皮的准确更新取决于微环境。肠道由密集的周围神经网络支配，该网络控制肠道生理学的各个方面。然而，神经元在调节上皮细胞再生中的作用仍然未知。
研究人员探究了肠道支配肾上腺素能神经对照射（IR）诱导损伤后上皮细胞修复的影响。研究人员观察到，IR后小肠中的肾上腺素能神经密度增加，而化学肾上腺素能去神经支配损害了上皮再生。单细胞RNA测序结果显示，去神经支配动物在IR后IL-22信号传导减少。药理和遗传学工具相结合，研究人员证明β-肾上腺素能受体信号传导促进IR后ILC3s产生IL-22，进而促进上皮再生。
这些结果揭示了对肠道再生非常重要的肾上腺素能-ILC3通路，为如何抵消胃肠癌患者放疗的副作用的添加新思路。
Highlights
• Adrenergic denervation impairs intestinal regeneration post IR-induced injury
• scRNA-seq reveals a reduction in epithelial IL-22 signaling upon denervation
• IL-22 levels from ILC3s post injury are regulated downstream of β-adrenergic receptors
• IL-22 mediates the effects of adrenergic nerves on intestinal regeneration
Summary
The intestinal epithelium has high intrinsic turnover rate, and the precise renewal of the epithelium is dependent on the microenvironment. The intestine is innervated by a dense network of peripheral nerves that controls various aspects of intestinal physiology. However, the role of neurons in regulating epithelial cell regeneration remains largely unknown. Here, we investigated the effects of gut-innervating adrenergic nerves on epithelial cell repair following irradiation (IR)-induced injury. We observed that adrenergic nerve density in the small intestine increased post IR, while chemical adrenergic denervation impaired epithelial regeneration. Single-cell RNA sequencing experiments revealed a decrease in IL-22 signaling post IR in denervated animals. Combining pharmacologic and genetic tools, we demonstrate that β-adrenergic receptor signaling drives IL-22 production from type 3 innate lymphoid cells (ILC3s) post IR, which in turn promotes epithelial regeneration. These results define an adrenergic-ILC3 axis important for intestinal regeneration.
文章来源：
Putianqi Wang, Noelyn Kljavin et al, Adrenergic nerves regulate intestinal regeneration through IL-22 signaling from type 3 innate lymphoid cells. DOI: 10.1016/j.stem.2023.07.013,Cell Stem Cell： 最新IF：25.269
