title: Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Galle-Treger
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Nisheel
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Ishwarya
authors.initials: I
authors.lastname: Sankaranarayanan
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Aron
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Hadi
authors.identifier: 0000-0002-8979-3769
authors.initials: H
authors.lastname: Maazi
authors.affiliation: Departments of Biological Science and Chemistry, University of Southern California, 1050 Childs Way RIH 201, Los Angeles, California 90089, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 1450 Biggy Street NRT 5509, Los Angeles, California 90033, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor