Thomas Christopher M, Peebles R Stokes
Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
Front Allergy. 2023 Jan 10;3:1094259. doi: 10.3389/falgy.2022.1094259. eCollection 2022.
The sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) regulate the effector functions of group 2 innate lymphoid cells (ILC2s) through 2 adrenergic receptor (ADRB2) and nicotinic/muscarinic cholinergic receptor signaling, respectively. To further maintain the critical balance between host-protective and pathogenic type 2 inflammation in the lungs, neuropeptides neuromedin B (NMB) and neuromedin U (NMU) function to suppress or promote ILC2 responses in synergy with IL-33/IL-25, respectively. Additionally, the release of ATP into the extracellular environment in response to cell death caused by challenge to the airway epithelial barrier quickly becomes converted into adenosine, which helps keep the inflammatory response in check by suppressing ILC2 responses. Besides neurotransmitter and neuropeptides derived from other cells, ILC2s further regulate allergic airway inflammation through the production of acetylcholine (ACh) and calcitonin gene-related peptide (CGRP). In this article we review the neuromodulation of ILC2s through cholinergic and adrenergic signaling, neuropeptides, and adenosine and its role in allergic airway inflammation. Furthermore, we discuss the potential clinical utility of targeting these pathways for therapeutic goals and address directions for future research.
交感神经系统（SNS）和副交感神经系统（PNS）分别通过β2肾上腺素能受体（ADRB2）和烟碱/毒蕈碱胆碱能受体信号传导来调节2型固有淋巴细胞（ILC2s）的效应器功能。为了进一步维持肺部宿主保护性和致病性2型炎症之间的关键平衡，神经肽神经介素B（NMB）和神经介素U（NMU）分别与IL-33/IL-25协同作用，发挥抑制或促进ILC2反应的功能。此外，由于气道上皮屏障受到挑战导致细胞死亡，ATP释放到细胞外环境中后会迅速转化为腺苷，腺苷通过抑制ILC2反应来帮助控制炎症反应。除了源自其他细胞的神经递质和神经肽外，ILC2s还通过产生乙酰胆碱（ACh）和降钙素基因相关肽（CGRP）进一步调节过敏性气道炎症。在本文中，我们综述了通过胆碱能和肾上腺素能信号传导、神经肽以及腺苷对ILC2s的神经调节作用及其在过敏性气道炎症中的作用。此外，我们还讨论了针对这些途径实现治疗目标的潜在临床应用，并阐述了未来研究的方向。
