title: Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.
abstract: Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma.
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Talbot
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Raja-Elie E
authors.initials: RE
authors.lastname: Abdulnour
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Burkett
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Seungkyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna 1030, Austria.
authors.forename: Shane J F
authors.initials: SJ
authors.lastname: Cronin
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Département de biologie, École Normale Supérieure de Cachan, Cachan 94230, France.
authors.forename: Maud A
authors.initials: MA
authors.lastname: Pascal
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Laedermann
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Simmie L
authors.initials: SL
authors.lastname: Foster
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Johnathan V
authors.initials: JV
authors.lastname: Tran
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lai
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Chiu
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Ghasemlou
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: DiBiase
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Roberson
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Von Hehn
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Busranour
authors.initials: B
authors.lastname: Agac
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Haworth
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna 1030, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Bean
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: blevy@partners.org.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: clifford.woolf@childrens.harvard.edu.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D056151:Airway Remodeling / Q000276:immunology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010047:Ovalbumin / Q000633:toxicity; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology*; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D016207:Cytokines; D015848:Interleukin-5; D049452:Green Fluorescent Proteins; C012647:QX-314; D014660:Vasoactive Intestinal Peptide; D010047:Ovalbumin; D005620:Freund's Adjuvant; D008012:Lidocaine; D002211:Capsaicin