Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease

Mattes, Joerg, Collison, Adam, Plank, Maximilian, Phipps, Simon and Foster, Paul S. (2009) Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proceedings of the National Academy of Sciences of the United States of America, 106 44: 18704-18709.


Author Mattes, Joerg
Collison, Adam
Plank, Maximilian
Phipps, Simon
Foster, Paul S.
Title Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease
Formatted title Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2009-11-03
Sub-type Article (original research)
DOI 10.1073/pnas.0905063106
Volume 106
Issue 44
Start page 18704
End page 18709
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted abstract Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (TH2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of TH2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished TH2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU.1 that alters TH2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.
Keyword Animal model
Asthma
Inflammation
MicroRNA
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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