RelB-Deficient dendritic cells promote the development of spontaneous allergic airway inflammation

Nair, Prema M., Starkey, Malcolm R., Haw, Tatt Jhong, Ruscher, Roland, Liu, Gang, Maradana, Muralidhara R., Thomas, Ranjeny, O’Sullivan, Brendan J., and Hansbro, Philip M. (2018) RelB-Deficient dendritic cells promote the development of spontaneous allergic airway inflammation. American Journal of Respiratory Cell and Molecular Biology, 58 (3). pp. 352-365.

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RelB is a member of the NF-κB family, which is essential for dendritic cell (DC) function and maturation. However, the contribution of RelB to the development of allergic airway inflammation (AAI) is unknown. Here, we identify a pivotal role for RelB in the development of spontaneous AAI that is independent of exogenous allergen exposure. We assessed AAI in two strains of RelB-deficient (RelB−/−) mice: one with a targeted deletion and one expressing a major histocompatibility complex transgene. To determine the importance of RelB in DCs, RelB-sufficient DCs (RelB+/+ or RelB−/−) were adoptively transferred into RelB−/− mice. Both strains had increased pulmonary inflammation compared with their respective wild-type (RelB+/+) and heterozygous (RelB+/−) controls. RelB−/− mice also had increased inflammatory cell influx into the airways, levels of chemokines (CCL2/3/4/5/11/17 and CXCL9/10/13) and T-helper cell type 2–associated cytokines (IL-4/5) in lung tissues, serum IgE, and airway remodeling (mucus-secreting cell numbers, collagen deposition, and epithelial thickening). Transfer of RelB+/− CD11c+ DCs into RelB−/− mice decreased pulmonary inflammation, with reductions in lung chemokines, T-helper cell type 2–associated cytokines (IL-4/5/13/25/33 and thymic stromal lymphopoietin), serum IgE, type 2 innate lymphoid cells, myeloid DCs, γδ T cells, lung Vβ13+ T cells, mucus-secreting cells, airway collagen deposition, and epithelial thickening. These data indicate that RelB deficiency may be a key pathway underlying AAI, and that DC-encoded RelB is sufficient to restore control of this inflammation.

Item ID: 60654
Item Type: Article (Research - C1)
ISSN: 1535-4989
Keywords: allergic airway disease; dendritic cells; RelB
Copyright Information: Copyright © 2018 by the American Thoracic Society
Funders: National Health and Medical Research Council (NHMRC), University of Newcastle (UoN), Australian Research Council (ARC), Queensland Government (QG), Arthritis Queensland (AQ)
Projects and Grants: NHMRC Early Career Research Fellowship, NHMRC Principal Research Fellowship, UoN Brawn Fellowship, ARC Future Fellowship, QG Smart State Fellowship
Date Deposited: 23 Oct 2019 00:59
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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