Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

Nat Commun. 2016 Oct 18:7:13202. doi: 10.1038/ncomms13202.

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.

Publication types

  • Research Support, N.I.H., Extramural

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*

Substances

  • Cytokines
  • Nicotinic Agonists
  • alpha7 Nicotinic Acetylcholine Receptor