FcεR1-expressing nociceptors trigger allergic airway inflammation.

Autor: Crosson T; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Wang JC; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Doyle B; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Merrison H; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Balood M; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Parrin A; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Pascal M; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Mindt BC; McGill University Research Center on Complex Traits, Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada., Seehus CR; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Ozcan A; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Huang X; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Semenara E; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Lai NYY; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Majdoubi A; Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Quebec, Canada., Abdulnour RE; Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., Rajchgot T; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Rafei M; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada., Foster SL; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass., Thibodeau J; Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Quebec, Canada., Fritz JH; McGill University Research Center on Complex Traits, Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada., Levy BD; Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., Woolf CJ; F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass; Department of Neurobiology, Harvard Medical School, Boston, Mass. Electronic address: clifford.woolf@childrens.harvard.edu., Talbot S; Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec, Canada. Electronic address: sebastien.talbot@umontreal.ca.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2021 Jun; Vol. 147 (6), pp. 2330-2342. Date of Electronic Publication: 2021 Jan 13.
DOI: 10.1016/j.jaci.2020.12.644
Abstrakt: Background: Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice.
Objective: We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure.
Methods: We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor-specific FcεR1γ knockdown (TRPV1 Cre ::FcεR1γ fl/fl ) mice to assess whether this targeted invalidation would affect the severity of allergic inflammation in response to allergen challenges.
Results: Lung-innervating jugular nodose complex ganglion neurons express the high-affinity IgE receptor FcεR1, the levels of which increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE-allergen immune complexes, through the release of substance P from their peripheral terminals, directly amplifies T H 2 cell influx and polarization in the airways. Allergic airway inflammation is decreased in TRPV1 Cre ::FcεR1γ fl/fl mice and in FcεR1α -/- mice into which bone marrow has been transplanted. Finally, increased in vivo circulating levels of IgE following allergen sensitization enhances the responsiveness of FcεR1 to immune complexes in both mouse jugular nodose complex ganglion neurons and human induced pluripotent stem cell-derived nociceptors.
Conclusions: Allergen sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1-expressing vagal sensory neurons, and T H 2 cells, which helps to both initiate and amplify allergic airway inflammation. These data highlight a novel target for reducing allergy, namely, FcεR1γ expressed by nociceptors.
(Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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