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Published ahead of print on June 28, 2007, doi:10.1165/rcmb.2007-0087OC

Am. J. Respir. Cell Mol. Biol., Volume 37, Number 5, November 2007, 553-561

A more recent version of this article appeared on November 1, 2007
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Submitted on March 14, 2007
Revised on June 26, 2007

Spatial Interactions Between Dendritic Cells and Sensory Nerves in Allergic Airway Inflammation

Tibor Z Veres1, Sabine Rochlitzer1, Marina Shevchenko1, Barbara Fuchs1, Frauke Prenzler1, Christina Nassenstein1, Axel Fischer2, Lutz Welker3, Olaf Holz3, Meike Muller1, Norbert Krug1, and Armin Braun1*

1 Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany, 2 Clinical Research Unit of Allergy, Humboldt University, Charite School of Medicine, Charite Campus-Virchow, Berlin, Germany, 3 Cytological Laboratory, Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Grosshansdorf, Germany

* To whom correspondence should be addressed. E-mail: armin.braun{at}item.fraunhofer.de.

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.




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