Functional differences in airway dendritic cells determine susceptibility to IgE-sensitization.

Leffler, Jonatan; Mincham, Kyle T; Mok, Danny; Blank, Fabian; Holt, Patrick G; Stumbles, Philip A; Strickland, Deborah H (2018). Functional differences in airway dendritic cells determine susceptibility to IgE-sensitization. Immunology and cell biology, 96(3), pp. 316-329. Wiley 10.1111/imcb.12005

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Respiratory IgE-sensitization to innocuous antigens increases the risk for developing diseases such as allergic asthma. Dendritic cells (DC) residing in the airways orchestrate the immune response following antigen exposure and their ability to sample and present antigens to naïve T cells in airway draining lymph nodes contributes to allergen-specific IgE-sensitization. In order to characterize inhaled antigen capture and presentation by DC subtypes in vivo, we used an adjuvant-free respiratory sensitization model using two genetically distinct rat strains, one of which is naturally resistant and the other naturally susceptible to allergic sensitization. Upon multiple exposures to ovalbumin (OVA), the susceptible strain developed OVA-specific IgE and airway inflammation, whereas the resistant strain did not. Using fluorescently tagged OVA and flow cytometry, we demonstrated significant differences in antigen uptake efficiency and presentation associated with either IgE-sensitization or resistance to allergen exposures in respective strains. We further identified CD4 conventional DC (cDC) as the subset involved in airway antigen sampling in both strains, however, CD4 cDC in the susceptible strain were less efficient in OVA sampling and displayed increased MHC-II expression compared with the resistant strain. This was associated with generation of an exaggerated Th2 response and a deficiency of airway regulatory T cells in the susceptible strain. These data suggest that subsets of cDC are able to induce either sensitization or resistance to inhaled antigens as determined by genetic background, which may provide an underlying basis for genetically determined susceptibility to respiratory allergic sensitization and IgE production in susceptible individuals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

UniBE Contributor:

Blank, Fabian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1440-1711

Publisher:

Wiley

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

04 Feb 2019 18:20

Last Modified:

12 Jun 2019 08:58

Publisher DOI:

10.1111/imcb.12005

PubMed ID:

29363184

Uncontrolled Keywords:

Adaptive immunity CD4-positive T cells T cells allergy antigen presentation dendritic cells immunological disorders immunology inflammatory diseases innate immune cells lymphocytes mucosal immunology regulatory T cells

BORIS DOI:

10.7892/boris.123041

URI:

https://boris.unibe.ch/id/eprint/123041

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