Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/807974
- Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease
Foster, Paul S.
- The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
- 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.
- Proceedings of the National Academy of Sciences of the United States of America Vol. 106, Issue 44, p. 18704-18709
- Publisher Link
- National Academy of Sciences
- Resource Type
- journal article