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

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Title: Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.
Authors: Mattes, Joerg1,2 joerg.mattes@newcastle.edu.au, Collison, Adam1,3, Plank, Maximilian1,3, Phipps, Simon3, Foster, Paul S.3 paul.foster@newcastle.edu.au
Source: Proceedings of the National Academy of Sciences of the United States of America. 11/3/2009, Vol. 106 Issue 44, p18704-18709. 6p. 4 Graphs.
Subjects: Asthma, House dust mites, Th2 cells, Antigens, RNA, Natural immunity, Transcription factors
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. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
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. [ABSTRACT FROM AUTHOR]
ISSN:00278424
DOI:10.1073/pnas.0905063106