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

Abstract:

:Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 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 T(H)2 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 T(H)2 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.

authors

Mattes J,Collison A,Plank M,Phipps S,Foster PS

doi

10.1073/pnas.0905063106

subject

Has Abstract

pub_date

2009-11-03 00:00:00

pages

18704-9

issue

44

eissn

0027-8424

issn

1091-6490

pii

0905063106

journal_volume

106

pub_type

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