An off switch for helminth immunity Group 2 innate lymphoid cells (ILC2s) are involved in responses to helminths, viruses, and allergens. Moriyama et al. found that ILC2s interact with the nervous system to modulate helminth immunity. ILC2s from the small intestine expressed the β2-adrenergic receptor (β2AR), which normally interacts with the neurotransmitter epinephrine. Inactivating β2AR resulted in lower helminth burden and more ILC2s, eosinophils, and type 2 cytokine production in mice. Conversely, treatment of helminth-infected mice with a β2AR agonist enhanced worm burden and reduced proliferation of ILC2s. Thus, β2AR negatively regulates ILC2-driven protective immunity. Science, this issue p. 1056 A neuronally derived regulatory circuit limits ILC2-dependent type 2 inflammation in the mouse intestine during helminth infection. The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β2-adrenergic receptor (β2AR) and colocalize with adrenergic neurons in the intestine. β2AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β2AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β2AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation.

中文翻译：

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β2-肾上腺素能受体介导的第 2 组先天淋巴细胞反应的负调节

蠕虫免疫的关闭开关 第 2 组先天淋巴细胞 (ILC2) 参与对蠕虫、病毒和过敏原的反应。森山等人。发现 ILC2s 与神经系统相互作用以调节蠕虫免疫。来自小肠的 ILC2 表达 β2-肾上腺素能受体 (β2AR)，它通常与神经递质肾上腺素相互作用。灭活 β2AR 导致小鼠蠕虫负担降低，ILC2、嗜酸性粒细胞和 2 型细胞因子产生更多。相反，用 β2AR 激动剂治疗蠕虫感染的小鼠会增加蠕虫负担并减少 ILC2 的增殖。因此，β2AR 负向调节 ILC2 驱动的保护性免疫。科学，这个问题 p。1056 神经元衍生的调节回路限制了蠕虫感染期间小鼠肠道中 ILC2 依赖性 2 型炎症。2 型炎症反应是由各种环境和感染性刺激引起的。尽管最近的研究将第 2 组先天淋巴细胞 (ILC2) 确定为 2 型细胞因子的有效来源，但控制 ILC2 反应的分子途径尚未完全确定。在这里，我们证明小鼠 ILC2s 表达 β2-肾上腺素能受体 (β2AR) 并与肠道中的肾上腺素能神经元共定位。β2AR 缺乏导致肠和肺组织中过度的 ILC2 反应和 2 型炎症。相反，β2AR激动剂治疗与ILC2反应受损和体内炎症减少有关。从机制上讲，我们证明 β2AR 途径是通过抑制细胞增殖和效应子功能对 ILC2 反应的细胞内在负调节因子。总的来说，