Title: Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity.
Authors: Galle-Treger, Lauriane; Suzuki, Yuzo; Patel, Nisheel; Sankaranarayanan, Ishwarya; Aron, Jennifer L; Maazi, Hadi; Chen, Lin; Akbari, Omid
Published In Nat Commun, (2016 10 18)
Abstract: 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.
PubMed ID: 27752043
MeSH Terms: Animals; Asthma/drug therapy; Asthma/metabolism; Cells, Cultured; Cytokines/metabolism; Disease Models, Animal; Humans; Lymphocytes/metabolism*; Mice, Inbred BALB C; Mice, Knockout; Nicotinic Agonists/pharmacology*; Respiratory Hypersensitivity/drug therapy*; Respiratory Hypersensitivity/metabolism; alpha7 Nicotinic Acetylcholine Receptor/metabolism*