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Neuron. 2015 Jul 15;87(2):341-54. doi: 10.1016/j.neuron.2015.06.007. Epub 2015 Jun 25.

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

Author information

1
FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
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.
4
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.
5
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.
6
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna 1030, Austria.
7
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
8
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
9
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.
10
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.

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.

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PMID:
26119026
PMCID:
PMC4506220
DOI:
10.1016/j.neuron.2015.06.007
[Indexed for MEDLINE]
Free PMC Article

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