- Title
- RelB-deficient dendritic cells promote the development of spontaneous allergic airway inflammation
- Creator
- Nair, Prema M.; Starkey, Malcolm R.; Haw, Tatt Jhong; Ruscher, Roland; Liu, Gang; Maradana, Muralidhara R.; Thomas, Ranjeny; O'Sullivan, Brendan J.; Hansbro, Philip M.
- Relation
- American Journal of Respiratory Cell and Molecular Biology Vol. 58, Issue 3, p. 352-365
- Publisher Link
- http://dx.doi.org/10.1165/rcmb.2017-0242oc
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2018
- Description
- RelB is a member of the NF-κB family that 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, independent of exogenous allergen exposure.We assessed AAI in two strains of RelB-deficient (RelB-/-) mice, one with a targeted deletion and another mutant expressing an major histocompatibility complex (MHC) 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 to 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, CXCL9/10/13) and Th2-associated cytokines (IL-4/5) in lung tissues, serum IgE and airway remodelling (mucus secreting cell numbers (MSCs), collagen deposition and epithelial thickening). Transfer of RelB-/- CD11c⁺ DCs to RelB-/- mice decreased pulmonary inflammation, with reduced lung chemokine and Th2-associated cytokine (IL-4/5/13/25/33, thymic stromal lymphopoietin) levels, serum IgE, numbers of type 2 innate lymphoid cells, myeloid DCs, γδ T cells and lung Vß13⁺ T cells, MSCs, 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.
- Subject
- allergic airway disease; dendritic cells; RelB
- Identifier
- http://hdl.handle.net/1959.13/1390552
- Identifier
- uon:33081
- Identifier
- ISSN:1044-1549
- Language
- eng
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