Cytokines reprogram airway sensory neurons in asthma
Summary: Nociceptor neurons play a crucial role in maintaining the body’s homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensi...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724013962 |
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| author | Theo Crosson Shreyas Bhat Jo-Chiao Wang Clara Salaun Eleanne Fontaine Katiane Roversi Herbert Herzog Moutih Rafei Rikard Blunck Sebastien Talbot |
| author_facet | Theo Crosson Shreyas Bhat Jo-Chiao Wang Clara Salaun Eleanne Fontaine Katiane Roversi Herbert Herzog Moutih Rafei Rikard Blunck Sebastien Talbot |
| author_sort | Theo Crosson |
| collection | DOAJ |
| description | Summary: Nociceptor neurons play a crucial role in maintaining the body’s homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we investigate the changes in the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identify a specific class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. In the ovalbumin mouse model of allergic airway inflammation, these neurons undergo significant reprogramming characterized by the upregulation of the neuropeptide Y (NPY) receptor Npy1r. A screening of cytokines and neurotrophins reveals that interleukin 1β (IL-1β), IL-13, and brain-derived neurotrophic factor (BDNF) drive part of this reprogramming. IL-13 triggers Npy1r overexpression in nociceptors via the JAK/STAT6 pathway. In parallel, NPY is released into the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. Single-cell RNA sequencing of lung immune cells reveals that a cell-specific knockout of NPY1R in nociceptor neurons in asthmatic mice altered T cell infiltration. Opposite findings are observed in asthmatic mice in which nociceptor neurons are chemically ablated. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, while a compensatory mechanism involving NPY1R limits the activity of nociceptor neurons. |
| format | Article |
| id | doaj-art-b16f16af8c9c4ad9adb450983f50d36c |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-b16f16af8c9c4ad9adb450983f50d36c2024-12-11T05:56:08ZengElsevierCell Reports2211-12472024-12-014312115045Cytokines reprogram airway sensory neurons in asthmaTheo Crosson0Shreyas Bhat1Jo-Chiao Wang2Clara Salaun3Eleanne Fontaine4Katiane Roversi5Herbert Herzog6Moutih Rafei7Rikard Blunck8Sebastien Talbot9Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaCentre Interdisciplinaire sur le Cerveau et l’Apprentissage, Université de Montréal, Montreal, QC, Canada; Département de Physique, Université de Montréal, Montreal, QC, CanadaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaGarvan Institute of Medical Research, Darlinghurst, NSW, AustraliaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaCentre Interdisciplinaire sur le Cerveau et l’Apprentissage, Université de Montréal, Montreal, QC, Canada; Département de Physique, Université de Montréal, Montreal, QC, CanadaDepartment of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden; Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada; Corresponding authorSummary: Nociceptor neurons play a crucial role in maintaining the body’s homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we investigate the changes in the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identify a specific class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. In the ovalbumin mouse model of allergic airway inflammation, these neurons undergo significant reprogramming characterized by the upregulation of the neuropeptide Y (NPY) receptor Npy1r. A screening of cytokines and neurotrophins reveals that interleukin 1β (IL-1β), IL-13, and brain-derived neurotrophic factor (BDNF) drive part of this reprogramming. IL-13 triggers Npy1r overexpression in nociceptors via the JAK/STAT6 pathway. In parallel, NPY is released into the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. Single-cell RNA sequencing of lung immune cells reveals that a cell-specific knockout of NPY1R in nociceptor neurons in asthmatic mice altered T cell infiltration. Opposite findings are observed in asthmatic mice in which nociceptor neurons are chemically ablated. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, while a compensatory mechanism involving NPY1R limits the activity of nociceptor neurons.http://www.sciencedirect.com/science/article/pii/S2211124724013962CP: ImmunologyCP: Neuroscience |
| spellingShingle | Theo Crosson Shreyas Bhat Jo-Chiao Wang Clara Salaun Eleanne Fontaine Katiane Roversi Herbert Herzog Moutih Rafei Rikard Blunck Sebastien Talbot Cytokines reprogram airway sensory neurons in asthma Cell Reports CP: Immunology CP: Neuroscience |
| title | Cytokines reprogram airway sensory neurons in asthma |
| title_full | Cytokines reprogram airway sensory neurons in asthma |
| title_fullStr | Cytokines reprogram airway sensory neurons in asthma |
| title_full_unstemmed | Cytokines reprogram airway sensory neurons in asthma |
| title_short | Cytokines reprogram airway sensory neurons in asthma |
| title_sort | cytokines reprogram airway sensory neurons in asthma |
| topic | CP: Immunology CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724013962 |
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