title: Spatial interactions between dendritic cells and sensory nerves in allergic airway inflammation.
abstract: 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 nonsensitized 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, human leukocyte antigen DR-positive mucosal dendritic cells were found in the close proximity of sensory nerves and neuroepithelial cells. These results provide morphologic evidence of the interactions between dendritic cells and the neural network of the airways at multiple anatomical sites.
authors.affiliation: Department of Immunology, Allergology and Immunotoxicology, Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Tibor Z
authors.initials: TZ
authors.lastname: Veres
authors.forename: Sabine
authors.initials: S
authors.lastname: Rochlitzer
authors.forename: Marina
authors.initials: M
authors.lastname: Shevchenko
authors.forename: Barbara
authors.initials: B
authors.lastname: Fuchs
authors.forename: Frauke
authors.initials: F
authors.lastname: Prenzler
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.forename: Axel
authors.initials: A
authors.lastname: Fischer
authors.forename: Lutz
authors.initials: L
authors.lastname: Welker
authors.forename: Olaf
authors.initials: O
authors.lastname: Holz
authors.forename: Meike
authors.initials: M
authors.lastname: Müller
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D018397:Equidae; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009475:Neurons, Afferent / Q000276:immunology* / Q000473:pathology; D010525:Peripheral Nerves / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D012137:Respiratory System / Q000294:innervation* / Q000473:pathology