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Spatial interactions between dendritic cells and sensory nerves in allergic airway inflammation

Epub ahead of print on June 28, 2007
: Veres, T.Z.; Rochlitzer, S.; Shevchenkom, M.; Fuchs, B.; Prenzler, F.; Nassenstein, C.; Fischer, A.; Welker, L.; Holz, O.; Müller, M.; Krug, N.; Braun, A.


American journal of respiratory cell and molecular biology 37 (2007), No.5, pp.553-561
ISSN: 1044-1549
ISSN: 1535-4989
Journal Article
Fraunhofer ITEM ()
dentritic cell; sensory nerve; allergic airway inflammation; neuroimmune interaction; Asthma

Neuroimmune interactions play a critical role in the pathogenesis of asthma. Symptoms like wheezing and cough have been attributed to neural dysregulation, whereas sensitization and the induction of allergic inflammation have been linked with the activity of dendritic cells. Neuropeptides were previously shown to control dendritic cell function in vitro, suggesting interactions between dendritic cells and sensory nerves. Here we characterized the anatomical basis of the interactions between dendritic cells and nerves in the airways of mice and monitored the changes during allergic inflammation. Airway microdissection, whole-mount immunohistology and confocal microscopy were used for the three-dimensional quantitative mapping of airway nerves and dendritic cells along the main axial pathway of non-sensitized versus ovalbumin-sensitized and challenged CD11c-Enhanced Yellow Fluorescent Protein (CD11c-EYFP) transgenic mice. CD11c-EYFP positive airway mucosal dendritic cells were contacted by Calcitonin Gene-Related Peptide immunoreactive sensory fibers and their co-localization increased in allergic inflammation. Moreover, Protein Gene Product 9.5 positive neuroepithelial bodies and airway ganglia were associated with dendritic cells. In human airways, HLA-DR positive mucosal dendritic cells were found in the close proximity of sensory nerves and neuroepithelial cells. These results provide morphological evidence of the interactions between dendritic cells and the neural network of the airways at multiple anatomical sites.