Journal Article

Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

Akbari, Omid, Galle-Treger, Lauriane, Suzuki, Yuzo, Patel, Nisheel, Chen, Lin, Aron, Jennifer L., Maazi, Hadi, Sankaranarayanan, Ishwarya

2016

Overview

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. Airway hyperreactivity is driven by type 2 cytokines produced by ILC2 and Th2 cells. Here the authors show that an α7-nicotinic receptor agonist (GTS-21) inhibits ILC2 responses and is therapeutic against Alternaria -induced airway hyperreactivity in a humanized mouse model.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/21 / 13/31 / 13/51 / 14/63 / 38/90 / 631/250/2504/2506 / 64/60 / 692/699/1785/31 / 82/1 / Antigens / Asthma / Crystal structure / Cytokines / Humanities and Social Sciences / Hypersensitivity / Kinases / Ligands / multidisciplinary / Neurological disorders / Pathogenesis / Phosphorylation / Science / Science (multidisciplinary)