Alcohol-mediated susceptibility to lung fibrosis is associated with group 2 innate lymphoid cells in mice.
Alcohol-mediated susceptibility to lung fibrosis is associated with group 2 innate lymphoid cells in mice.
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酒精介导的肺纤维化易感性与小鼠2组先天淋巴样细胞有关。
DOI：
10.3389/fimmu.2023.1178498
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
长期饮酒会导致急性肺损伤，并损害免疫功能。然而，所涉及的机制还不完全清楚。在这里，我们表明酒精喂养通过调节2型先天免疫反应，特别是通过第二组先天淋巴样细胞(ILC2s)来增强博莱霉素诱导的肺纤维化和炎症。神经免疫相互作用已成为肺部炎症的关键调节因子。我们发现，饮酒导致ILC2积聚，并减少降钙素基因相关肽(CGRP)的产生，主要由感觉神经和肺神经内分泌细胞(PNECs)释放。CGRP在体内有效地抑制了酒精驱动的2型细胞因子信号。迷走神经节TRPV1+传入通过释放CGRP介导免疫抑制。TRPV1受体失活可增强博莱霉素诱导的纤维化。此外，缺乏CGRP受体的小鼠的肺部炎症和纤维化增加，2型细胞因子产生，以及对酒精喂养的夸大反应。总之，这些数据表明，饮酒调节CGRP和ILC2的相互作用，而ILC2是肺部炎症和纤维化的关键贡献者。
Chronic alcohol ingestion promotes acute lung injury and impairs immune function. However, the mechanisms involved are incompletely understood. Here, we show that alcohol feeding enhances bleomycin-induced lung fibrosis and inflammation via the regulation of type 2 innate immune responses, especially by group 2 innate lymphoid cells (ILC2s). Neuroimmune interactions have emerged as critical modulators of lung inflammation. We found alcohol consumption induced the accumulation of ILC2 and reduced the production of the neuropeptide calcitonin gene-related peptide (CGRP), primarily released from sensory nerves and pulmonary neuroendocrine cells (PNECs). CGRP potently suppressed alcohol-driven type 2 cytokine signals in vivo. Vagal ganglia TRPV1+ afferents mediated immunosuppression occurs through the release of CGRP. Inactivation of the TRPV1 receptor enhanced bleomycin-induced fibrosis. In addition, mice lacking the CGRP receptor had the increased lung inflammation and fibrosis and type 2 cytokine production as well as exaggerated responses to alcohol feeding. Together, these data indicate that alcohol consumption regulates the interaction of CGRP and ILC2, which is a critical contributor of lung inflammation and fibrosis.