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Neuroimmune crosstalk in asthma: dual role of the neurotrophin receptor p75NTR.

AbstractBACKGROUND:
Neurotrophins have been implicated in the pathogenesis of asthma because of their ability to induce airway inflammation and to promote hyperreactivity of sensory neurons, which reflects an important mechanism in the pathogenesis of airway hyperreactivity. Neurotrophins use a dual-receptor system consisting of Trk-receptor tyrosine kinases and the structurally unrelated p75NTR. Previous studies revealed an important role of p75NTR in the pathogenesis of allergic asthma.
OBJECTIVES:
The aim of the study was to investigate the precise mechanisms of neurotrophins in neuroimmune interaction, which can lead to both airway inflammation and sensory nerve hyperreactivity in vivo.
METHODS:
Mice selectively expressing p75NTR in immune cells or nerves, respectively, were generated. After sensitization and allergen provocation, hyperreactivity of sensory nerves was tested in response to capsaicin. Airway inflammation was analyzed on the basis of differential cell counts and cytokine levels in bronchoalveolar lavage fluids.
RESULTS:
Allergic mice selectively expressing p75NTR in immune cells showed normal inflammation but no sensory nerve hyperreactivity, whereas mice selectively expressing p75NTR in nerve cells had a diminished inflammation and a distinct sensory nerve hyperreactivity.
CONCLUSION:
Our data indicate that p75NTR plays a dual role by promoting hyperreactivity of sensory nerves and airway inflammation. Additionally, our study provides experimental evidence that development of sensory nerve hyperreactivity depends on an established airway inflammation in asthma. In contrast, development of airway inflammation seems to be independent from sensory nerve hyperreactivity.
CLINICAL IMPLICATIONS:
Because of its dual function, antagonization of p75NTR-mediated signals might be a novel approach in asthma therapy.
AuthorsChristina Nassenstein, Thomas Kammertoens, Tibor Zoltan Veres, Wolfgang Uckert, Emma Spies, Barbara Fuchs, Norbert Krug, Armin Braun
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 120 Issue 5 Pg. 1089-96 (Nov 2007) ISSN: 1097-6825 [Electronic] United States
PMID17716721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor
  • TNFRSF16 protein, mouse
Topics
  • Afferent Pathways (immunology)
  • Animals
  • Asthma (immunology)
  • Bronchoalveolar Lavage Fluid (immunology)
  • Inflammation (immunology)
  • Mice
  • Mice, Knockout
  • Nerve Growth Factors (analysis, metabolism)
  • Neurons, Afferent (immunology)
  • Receptors, Nerve Growth Factor (genetics, physiology)

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