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Blockade of dopamine D 1‐like receptor signalling protects mice against OVA ‐induced acute asthma by inhibiting B ‐cell activating transcription factor signalling and T h17 function
Author(s) -
Gong Subo,
Li Jinxiu,
Ma Libing,
Li Keng,
Zhang Li,
Wang Guyi,
Liu Yi,
Ji Xiaoying,
Liu Xiaokun,
Chen Ping,
Ouyang Ruoyun,
Zhang Shu,
Zhou Zhiguang,
Wang CongYi,
Xiang Xudong,
Yang Yu
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12549
Subject(s) - immunology , receptor , blockade , medicine , transcription factor , biology , biochemistry , gene
Previous studies have consistently demonstrated that dopamine D 1‐like receptor ( D 1‐like‐ R ) signalling is implicated in the pathogenesis of experimental autoimmune encephalomyelitis and type I diabetes. Given that allergic asthma shares certain disease aetiology similarities with autoimmune diseases, we conducted studies in OVA ‐induced mice aiming to address the impact of D 1‐like‐ R signalling on the pathogenesis of allergic asthma. It was noted that blockade of D 1‐like‐ R signalling provided protection for mice against OVA ‐induced acute asthma. Particularly, treatment of OVA ‐induced mice with SCH 23390, a D 1‐like‐ R antagonist, significantly attenuated inflammatory infiltration in the airways along with repressed goblet cell hyperplasia and mucus production, as well as airway resistance. By contrast, administration of SKF 83959, a D 1‐like‐ R agonist, displayed the opposite effect. Blockade of D 1‐like‐ R signalling impaired T h17 function, as manifested by a significant reduction of T h17 cells in the spleen and bronchoalveolar lavage fluid. Mechanistic studies revealed that D 1‐like‐ R signalling enhances B ‐cell activating transcription factor activity, which then transcribes the expression of ROR γt, a T h17 transcription factor; accordingly, D 1‐like‐ R signalling regulates T h17 differentiation to promote the development of allergic asthma. Taken together, the data obtained in the present suggest that blockade of D 1‐like‐ R signalling could be an effective therapeutic strategy for the prevention and treatment of allergic asthma in clinical practice.