Antagonism of microRNA-126 suppresses the effector function of T(H)2 cells and the development of allergic airways disease

作者：Mattes Joerg^*; Collison Adam; Plank Maximilian; Phipps Simon; Foster Paul S

来源：Proceedings of the National Academy of Sciences, 2009, 106(44): 18704-18709.

DOI：10.1073/pnas.0905063106

• animal model
• asthma
• inflammation
• microRNA
• T(H)2 cytokines

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.

• 出版日期2009-11-3