Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
Departments of Biological Science and Chemistry, University of Southern California, 1050 Childs Way RIH 201, Los Angeles, California 90089, USA.
Nat Commun. 2016 Oct 18;7:13202. doi: 10.1038/ncomms13202.
Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β. Additionally, the specific α7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that α7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma.
过敏性哮喘是一种复杂的慢性炎症性疾病，与气道高反应性（AHR）相关，并由 Th2 细胞因子分泌驱动。2 型固有淋巴细胞（ILC2s）产生大量 Th2 细胞因子，并有助于 AHR 的发展。在这里，我们表明 ILC2s 表达α7-烟碱型乙酰胆碱受体（α7nAChR），该受体被认为在几种炎症性疾病中具有抗炎作用。我们表明，α7nAChR 与 ILC2 上的特定激动剂结合可降低 ILC2 的效应功能，并抑制 ILC2 依赖性 AHR，同时降低 ILC2 关键转录因子 GATA-3 和关键炎症调节剂 NF-κB 的表达，并减少上游激酶 IKKα/β 的磷酸化。此外，特定的α7nAChR 激动剂可减少人源化 ILC2 小鼠模型中的细胞因子产生和 AHR。总之，我们的数据表明，ILC2 表达的α7nAChR 是治疗 ILC2 介导的哮喘的潜在治疗靶点。
Zotero 插件
