Innate lymphocytes maintain tissue homeostasis at mucosal barriers, with group 2 innate lymphoid cells (ILC2s) producing type 2 cytokines and controlling helminth infection. While the molecular understanding of ILC2 responses has advanced, the complexity of microenvironmental factors impacting ILC2s is becoming increasingly apparent. Herein, we used single-cell analysis to explore the diversity of gene expression among lung lymphocytes during helminth infection. Following infection, we identified a subset of ILC2s that preferentially expressed Il5-encoding interleukin (IL)-5, together with Calca-encoding calcitonin gene-related peptide (CGRP) and its cognate receptor components. CGRP in concert with IL-33 and neuromedin U (NMU) supported IL-5 but constrained IL-13 expression and ILC2 proliferation. Without CGRP signaling, ILC2 responses and worm expulsion were enhanced. Collectively, these data point to CGRP as a context-dependent negative regulatory factor that shapes innate lymphocyte responses to alarmins and neuropeptides during type 2 innate immune responses.

中文翻译：

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神经肽 CGRP 限制第 2 组先天淋巴细胞反应并抑制 2 型炎症。

先天性淋巴细胞在粘膜屏障处维持组织稳态，第 2 组先天性淋巴样细胞 (ILC2s) 产生 2 型细胞因子并控制蠕虫感染。虽然对 ILC2 反应的分子理解有所进步，但影响 ILC2 的微环境因素的复杂性正变得越来越明显。在此，我们使用单细胞分析来探索寄生虫感染期间肺淋巴细胞基因表达的多样性。感染后，我们确定了 ILC2 的一个子集，该子集优先表达编码 Il5 的白细胞介素 (IL)-5，以及编码 Calca 的降钙素基因相关肽 (CGRP) 及其同源受体成分。CGRP 与 IL-33 和神经调节素 U (NMU) 协同支持 IL-5，但限制 IL-13 表达和 ILC2 增殖。在没有 CGRP 信令的情况下，ILC2 响应和蠕虫驱逐得到增强。总的来说，这些数据表明 CGRP 是一种依赖于环境的负调节因子，它在 2 型先天免疫反应期间形成先天淋巴细胞对警报素和神经肽的反应。