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

Prema M. Nair, Malcolm R. Starkey, Tatt Jhong Haw, Roland Ruscher, Gang Liu, Muralidhara R. Maradana, Ranjeny Thomas, Brendan J. O'Sullivan, Philip M. Hansbro

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Abstract

RelB is a member of the NF-kB 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 (RelB2/2) 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 (RelB1/1 or RelB2/2) were adoptively transferred into RelB2/2 mice. Both strains had increased pulmonary inflammation compared with their respective wild-type (RelB1/1) and heterozygous (RelB1/2) controls. RelB2/2 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 RelB1/2 CD11c1 DCs into RelB2/2 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, gd T cells, lung Vb131 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.

Original languageEnglish
Pages (from-to)352-365
Number of pages14
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume58
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

Keywords

  • Allergic airway disease
  • Dendritic cells
  • RelB

Cite this

Nair, P. M., Starkey, M. R., Haw, T. J., Ruscher, R., Liu, G., Maradana, M. R., Thomas, R., O'Sullivan, B. J., & Hansbro, P. M. (2018). RelB-deficient dendritic cells promote the development of spontaneous allergic airway inflammation. American Journal of Respiratory Cell and Molecular Biology, 58(3), 352-365. https://doi.org/10.1165/rcmb.2017-0242OC