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

Veres, Tibor Z.; Rochlitzer, Sabine; Shevchenko, Marina; Fuchs, Barbara; Prenzler, Frauke; Nassenstein, Christina; Fischer, Axel; Welker, L; Holz, Olaf; Müller, Meike; Krug, Norbert; Braun, Armin

doi:10.1165/rcmb.2007-0087oc

Cited by 71 publications

(70 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may also be that ozone has subtle effects on tissue leukocytes near airways or recruited to airways that could indirectly affect AHR through interaction with neural signaling. In a mouse model of allergic airways, dendritic cells have been found to have close proximity to airway nerves (38,39), but the functional significance is unknown. In the guinea pig, eosinophils have been shown to interfere with termination of airway neuromuscular signaling (40), but, to our knowledge, this mechanism has not been shown in other species.…”

Section: Discussionmentioning

confidence: 99%

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Auten¹,

Gilmour

Krantz

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (AHR) in offspring. To determine if exposure to diesel exhaust (DE) during pregnancy worsened postnatal ozone-induced AHR, timed pregnant C57BL/6 mice were exposed to DE (0.5 or 2.0 mg/m 3 ) 4 hours daily from Gestation Day 9-17, or received twice-weekly oropharyngeal aspirations of the collected DE particles (DEPs). Placentas and fetal lungs were harvested on Gestation Day 18 for cytokine analysis. In other litters, pups born to dams exposed to air or DE, or to dams treated with aspirated diesel particles, were exposed to filtered air or 1 ppm ozone beginning the day after birth, for 3 hours per day, 3 days per week for 4 weeks. Additional pups were monitored after a 4-week recovery period. Diesel inhalation or aspiration during pregnancy increased levels of placental and fetal lung cytokines. There were no significant effects on airway leukocytes, but prenatal diesel augmented ozone-induced elevations of bronchoalveolar lavage cytokines at 4 weeks. Mice born to the high-concentration dieselexposed dams had worse ozone-induced AHR, which persisted in the 4-week recovery animals. Prenatal diesel exposure combined with postnatal ozone exposure also worsened secondary alveolar crest development. We conclude that maternal inhalation of DE in pregnancy provokes a fetal inflammatory response that, combined with postnatal ozone exposure, impairs alveolar development, and causes a more severe and long-lasting AHR to ozone exposure.Keywords: diesel; fetal inflammation; ozone; airway hyperreactivity Increasing asthma prevalence among children in industrialized nations has stimulated a number of investigations focused on early life exposures to air pollutants (1). Maternal exposures to a variety of inhaled atmospheric pollutants, including side and mainstream tobacco smoke, diesel exhaust (DE), and ozone, have been linked in epidemiologic studies to asthma and other respiratory diseases in children (2-4). Animal models aimed at deciphering the mechanisms by which maternal exposures during pregnancy are linked to childhood asthma have largely focused on pathways relevant to allergic asthma (5).In addition to allergic sensitization, in utero exposure to air pollutants may also affect nonspecific pulmonary responses, such as airway hyperreactivity (AHR) (6). It has already been shown that fetal pulmonary inflammatory challenges are linked with impaired postnatal alveolar development (7-9), which affects airway stability and AHR (10). Previous studies have shown that maternal exposure to DE during pregnancy modified mouse placental cytokines relevant to airway inflammation (11), and lowered the threshold for AHR in ovalbuminsensitized offspring (12).We have previously shown that a standardized urban particulate delivered by oropharyngeal aspiration during pregnancy induced placental inflammatory cytokine expression and worsened neonatal ozone-induced...

show abstract

Section: Discussionmentioning

confidence: 99%

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Auten¹,

Gilmour

Krantz

et al. 2012

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…8,9 As proof for the existence of this mechanism, we previously demonstrated the close proximity between CD11c ϩ DCs and CGRP ϩ sensory nerves in the airway mucosa. 10 Neuropeptides released from adjacent sensory terminals might also affect the activation of T cells either directly 11 or by modulating the activity of DCs in contact with T cells.…”

Section: Interactions Between T Cells and Dendritic Cells In Thementioning

confidence: 99%

“…The tissue was processed as described earlier. 10 Briefly, the lungs were inflation-fixed with Zamboni's solution and the main axial pathways of each lobe were microdissected (see supplemental Figures S1A and S1B at http://ajp.amjpathol.org). The airways were then washed, permeabilized with 0.3% Triton X-100 in PBS and immunostained as whole-mounts.…”

Section: Tissue Processing and Whole-mount Immunostainingmentioning

confidence: 99%

Dendritic Cell-Nerve Clusters Are Sites of T Cell Proliferation in Allergic Airway Inflammation

Veres

Shevchenko

Krasteva

et al. 2009

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Interactions between T cells and dendritic cells in the airway mucosa precede secondary immune responses to inhaled antigen. The purpose of this study was to identify the anatomical locations where dendritic cell-T cell interactions occur, resulting in T cells activation by dendritic cells. In a mouse model of allergic airway inflammation, we applied whole-mount immunohistology and confocal microscopy to visualize dendritic cells and T cells together with nerves, epithelium, and smooth muscle in three dimensions. Proliferating T cells were identified by the detection of the incorporation of the nucleotide analogue 5-ethynyl-2-deoxyuridine into the DNA. We developed a novel quantification method that enabled the accurate determination of cell-cell contacts in a semiautomated fashion. Dendritic cell-T cell interactions occurred beneath the smooth muscle layer, but not in the epithelium. Approximately 10% of the dendritic cells were contacted by nerves, and up to 4% of T cells formed clusters with these dendritic cells. T cells that were clustered with nerve-contacting dendritic cells proliferated only in the airways of mice with allergic inflammation but not in the airways of negative controls. Taken together, these results suggest that during the secondary immune response, sensory nerves influence dendritic cell-driven T cell activation in the airway mucosa.

show abstract

“…DCs in these mice exhibit high Xuorescence, and are readily identiWable by both Xuorescence microscopy and Xow cytometry. These mice have not only greatly improved our understanding of the behavior of endogenous DCs in the LN (Lindquist et al 2004;Shakhar et al 2005), but also their roles in various models of infection (Aoshi et al 2008;Hapfelmeier et al 2008;Veres et al 2007). They also enabled the visualization of intestinal DCs (Flores-Langarica et al 2005) and the identiWcation of a previously uncharacterized population of DCs in the brain (Bulloch et al 2008).…”

Section: Lcs and Ddcs In The Skin In Vivo: Lessons From Confocal Micrmentioning

confidence: 99%

Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

View full text Add to dashboard Cite

Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.

show abstract

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

Cited by 71 publications

References 37 publications

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Dendritic Cell-Nerve Clusters Are Sites of T Cell Proliferation in Allergic Airway Inflammation

Visualizing dendritic cell migration within the skin

Contact Info

Product

Resources

About