MicroRNA-155 is essential for TH2-mediated allergen-induced eosinophilic inflammation in the lung

Background Allergic asthma is a chronic disease of the conducting airways characterized by T H 2 inflammation and tissue remodeling after exposure to inhaled allergens. Although the T H 2 profile is undisputed, the underlying molecular mechanisms leading to this abnormal T H 2 profile remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs that are important regulators of gene expression in the immune system. However, the role of miRNAs, specifically miR-155, in the regulation of allergic airway inflammation is unexplored. Objectives We sought to assess the contribution of miR-155 in a mouse model of allergic airway inflammation. Methods To investigate a role for miR-155 in the regulation of allergic inflammation in vivo , we used miR-155 knockout (KO) and wild-type (WT) mice sensitized and exposed to ovalbumin. Results miR-155 deficiency resulted in diminished eosinophilic inflammation and mucus hypersecretion in the lungs of allergen-sensitized and allergen-challenged mice compared with WT control animals. This was supported by a reduction in T H 2 cell numbers and airway T H 2 cytokine levels and complete abrogation of allergen-induced airway eotaxin-2/CCL24 and periostin levels in miR-155 KO mice. Intranasal instillation of eotaxin-2/CCL24 before allergen challenge partially restored airway eosinophilia in miR-155 KO mice, and adoptive transfer of CD4 + T cells resulted in a similar degree of airway eosinophilia in miR-155 KO and WT mice. Furthermore, the transcription factor PU.1, a negative regulator of T H 2 cytokine production, was upregulated in the airways of allergen-challenged miR-155 KO mice compared with WT mice. Conclusions Our data provides evidence that miR-155 contributes to the regulation of allergic airway inflammation by modulating T H 2 responses through the transcription factor PU.1.