Neuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation
Neuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation
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DOI：
10.1016/j.immuni.2019.06.009
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发表时间：
2019-10-15
期刊：
影响因子：
32.4
通讯作者：
O'Shea, John J.
中科院分区：
文献类型：
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作者：
Nagashima, Hiroyuki;Mahlakoiv, Tanel;O'Shea, John J.
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（ILC 2）产生2型细胞因子并控制蠕虫感染。虽然ILC 2反应的分子理解已经进步，但影响ILC 2的微环境因素的复杂性变得越来越明显。在此，我们使用单细胞分析来探讨蠕虫感染过程中肺淋巴细胞基因表达的多样性。感染后，我们确定了一个ILC 2的子集，优先表达IL-5编码白细胞介素（IL）-5，Ca/Ca编码降钙素基因相关肽（CGRP）及其同源受体成分。CGRP与IL-33和神经介肽U（NMU）一起支持IL-5，但抑制IL-13表达和ILC 2增殖。没有CGRP信号，ILC 2反应和蠕虫驱逐增强。总的来说，这些数据表明CGRP作为一种环境依赖性负调控因子，其在2型先天免疫应答期间形成对警报素和神经肽的先天淋巴细胞应答。
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 interleu kin (IL)-5, together with Ca/ca-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.