Bcl11b Regulates IL-17 Through the TGF-β/Smad Pathway in HDM-Induced Asthma.
10.4168/aair.2018.10.5.543
- Author:
Si CHEN
1
;
Yuting HAN
;
Hao CHEN
;
Jing WU
;
Min ZHANG
Author Information
1. Department of Immunology, Shenzhen University School of Medicine, Shenzhen, China. chensi@szu.edu.cn
- Publication Type:Original Article
- Keywords:
Asthma;
Bcl11b;
IL-17A
- MeSH:
Animals;
Asthma*;
Blotting, Western;
Cytokines;
Ectopic Gene Expression;
Enzyme-Linked Immunosorbent Assay;
Humans;
Inflammation;
Interleukin-13;
Interleukin-17*;
Interleukin-4;
Interleukin-5;
Interleukins;
Mice;
Phosphorylation;
Plasma;
Plasmids;
Polymerase Chain Reaction;
Pyroglyphidae;
RNA, Messenger;
T-Lymphocytes;
Transforming Growth Factors
- From:Allergy, Asthma & Immunology Research
2018;10(5):543-554
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: T helper (Th) 17 cells play a critical role in the development of asthma, but the underlying mechanism of how interleukin (IL)-17 is regulated in allergic airway inflammation is poorly understood. In this study, we investigated the impact of Bcl11b on Th17 response in asthma. METHODS: Blood samples from patients with mild asthma (MA) and severe asthma (SA) were collected. Expression of Bcl11b, IL-4, IL-5, IL-13, IL-17A and transforming growth factor (TGF)-β1 were determined in CD4+ T cells and plasma by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Relative mRNA and protein levels of Bcl11b, IL-17A and genes involved in the TGF/Smad signaling pathway were examined by PCR, ELISA and western blot analysis in house dust mite (HDM)-challenged mice. Ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes was achieved by nucleofection of Bcl11b expression plasmid. RESULTS: We found significantly decreased Bcl11b but increased IL-17A and TGF-β1 expression in patients with asthma and a strongly negative correlation between Bcl11b and these 2 cytokines in SA patients. Similar expression patterns of Bcl11b, IL-17A and TGF-β1 were also found in mice with HDM-induced allergic airway inflammation. We demonstrated further that Smad2/3 phosphorylation was increased in HDM-challenged mice and that ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes reduced Smad2 phosphorylation and IL-17 expression. CONCLUSIONS: Our findings demonstrate a potential effect of Bc111b in controlling IL-17-mediated inflammation in asthma and suggest that Bc111b may be a useful therapeutic target for asthma.
