title: Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation.
abstract: BACKGROUND
  IL-13, a cytokine secreted by T(H)2 lymphocytes and other cells, critically modulates allergic inflammation and tissue remodeling in allergic asthma. Although much is known about transcriptional regulation of IL-13, posttranscriptional regulation is poorly understood.
  
  
  OBJECTIVE
  Because many inflammatory pathways are known to be regulated by microRNAs, permitting a rapid and fine-tuned response, the role of microRNA-mediated regulation of IL-13 was investigated using both in vitro and in vivo studies.
  
  
  METHODS
  A combination of in silico approaches and in vitro transfections in A549 cells and primary cultured T cells was used to demonstrate the involvement of let-7 in IL-13 regulation. Furthermore, intranasal delivery of let-7 microRNA mimic in mice was performed to study its effects in allergic airway inflammatory conditions.
  
  
  RESULTS
  Using a combination of bioinformatics and molecular approaches, we demonstrate that the let-7 family of microRNAs regulates IL-13 expression. Induced levels of IL-13 in cultured T cells were inversely related to let-7 levels. In an IL-13-dependent murine model of allergic airway inflammation, we observed that inflammation was associated with a reduction in most of the members of the let-7 family. Exogenous administration of let-7 mimic to lungs of mice with allergic inflammation resulted in a decrease in IL-13 levels, resolution of airway inflammation, reduction in airway hyperresponsiveness, and attenuation of mucus metaplasia and subepithelial fibrosis.
  
  
  CONCLUSIONS
  Let-7 microRNAs inhibit IL-13 expression and represent a major regulatory mechanism for modulating IL-13 secretion in IL-13-producing cell types and thereby T(H)2 inflammation.
authors: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, Institute of Genomics and Integrative Biology (Unit of C.S.I.R.), Delhi, India.
authors: Manish
authors: M
authors: Kumar
authors: Tanveer
authors: T
authors: Ahmad
authors: Amit
authors: A
authors: Sharma
authors: Ulaganathan
authors: U
authors: Mabalirajan
authors: Ankur
authors: A
authors: Kulshreshtha
authors: Anurag
authors: A
authors: Agrawal
authors: Balaram
authors: B
authors: Ghosh