Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

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 alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with alpha 7nAChR 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-kappa B, and reducing phosphorylation of upstream kinase IKK alpha/beta. Additionally, the specific alpha 7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that alpha 7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma.