PMID- 26119026 OWN - NLM STAT- MEDLINE DCOM- 20150928 LR - 20211102 IS - 1097-4199 (Electronic) IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 87 IP - 2 DP - 2015 Jul 15 TI - Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation. PG - 341-54 LID - S0896-6273(15)00520-6 [pii] LID - 10.1016/j.neuron.2015.06.007 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Talbot, Sebastien AU - Talbot S AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Abdulnour, Raja-Elie E AU - Abdulnour RE AD - Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Burkett, Patrick R AU - Burkett PR AD - 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. FAU - Lee, Seungkyu AU - Lee S AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Cronin, Shane J F AU - Cronin SJ AD - 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. FAU - Pascal, Maud A AU - Pascal MA AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Departement de biologie, Ecole Normale Superieure de Cachan, Cachan 94230, France. FAU - Laedermann, Cedric AU - Laedermann C AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Foster, Simmie L AU - Foster SL AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Tran, Johnathan V AU - Tran JV AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Lai, Nicole AU - Lai N AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Chiu, Isaac M AU - Chiu IM AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Ghasemlou, Nader AU - Ghasemlou N AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - DiBiase, Matthew AU - DiBiase M AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Roberson, David AU - Roberson D AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Von Hehn, Christian AU - Von Hehn C AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Agac, Busranour AU - Agac B AD - FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Haworth, Oliver AU - Haworth O AD - Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Seki, Hiroyuki AU - Seki H AD - Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Penninger, Josef M AU - Penninger JM AD - IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna 1030, Austria. FAU - Kuchroo, Vijay K AU - Kuchroo VK AD - Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Bean, Bruce P AU - Bean BP AD - Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. FAU - Levy, Bruce D AU - Levy BD AD - 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. FAU - Woolf, Clifford J AU - Woolf CJ AD - 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. LA - eng GR - T32 HL007633/HL/NHLBI NIH HHS/United States GR - R37 NS039518/NS/NINDS NIH HHS/United States GR - R37NS039518/NS/NINDS NIH HHS/United States GR - P01-GM095467/GM/NIGMS NIH HHS/United States GR - R01 AI068084/AI/NIAID NIH HHS/United States GR - P01 GM095467/GM/NIGMS NIH HHS/United States GR - 5T32HL007633/HL/NHLBI NIH HHS/United States GR - F32 NS076297-01/NS/NINDS NIH HHS/United States GR - P01 NS072040/NS/NINDS NIH HHS/United States GR - P30 HD018655/HD/NICHD NIH HHS/United States GR - R01-HL122531/HL/NHLBI NIH HHS/United States GR - AI068084/AI/NIAID NIH HHS/United States GR - R01 HL122531/HL/NHLBI NIH HHS/United States GR - K22 AI114810/AI/NIAID NIH HHS/United States GR - F32 NS076297/NS/NINDS NIH HHS/United States GR - P01NS072040/NS/NINDS NIH HHS/United States GR - R56 AI068084/AI/NIAID NIH HHS/United States GR - P30-HD18655/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150625 PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Anesthetics, Local) RN - 0 (Cytokines) RN - 0 (Interleukin-5) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 21306-56-9 (QX-314) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - 9006-59-1 (Ovalbumin) RN - 9007-81-2 (Freund's Adjuvant) RN - 98PI200987 (Lidocaine) RN - S07O44R1ZM (Capsaicin) SB - IM CIN - Nat Rev Neurosci. 2015 Aug;16(8):444. PMID: 26174707 MH - Airway Remodeling/*immunology MH - Anesthetics, Local/pharmacology MH - Animals MH - Animals, Newborn MH - Capsaicin/pharmacology MH - Cytokines/metabolism MH - Disease Models, Animal MH - Freund's Adjuvant/toxicity MH - Green Fluorescent Proteins/genetics/metabolism MH - Interleukin-5/metabolism MH - Lidocaine/analogs & derivatives/pharmacology MH - Mice MH - Nociceptors/drug effects/metabolism/*physiology MH - Ovalbumin/toxicity MH - Respiratory Hypersensitivity/chemically induced/*immunology MH - Time Factors MH - Vasoactive Intestinal Peptide/metabolism PMC - PMC4506220 MID - NIHMS697736 COIS- The authors have declared that no conflicts of interest exist. EDAT- 2015/06/30 06:00 MHDA- 2015/09/29 06:00 PMCR- 2016/07/15 CRDT- 2015/06/30 06:00 PHST- 2014/11/05 00:00 [received] PHST- 2015/04/16 00:00 [revised] PHST- 2015/06/01 00:00 [accepted] PHST- 2015/06/30 06:00 [entrez] PHST- 2015/06/30 06:00 [pubmed] PHST- 2015/09/29 06:00 [medline] PHST- 2016/07/15 00:00 [pmc-release] AID - S0896-6273(15)00520-6 [pii] AID - 10.1016/j.neuron.2015.06.007 [doi] PST - ppublish SO - Neuron. 2015 Jul 15;87(2):341-54. doi: 10.1016/j.neuron.2015.06.007. Epub 2015 Jun 25.