title: MicroRNA-155 is essential for T(H)2-mediated allergen-induced eosinophilic inflammation in the lung.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Malmhäll
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sahar
authors.initials: S
authors.lastname: Alawieh
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Sjöstrand
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Bossios
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Eldh
authors.affiliation: Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: madeleine.radinger@gu.se.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Rådinger
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D054423:Chemokine CCL24 / Q000276:immunology / Q000633:toxicity*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000485:Allergens; D054423:Chemokine CCL24; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C515485:Ccl24 protein, mouse; C532623:Mirn155 microRNA, mouse
keywords: MicroRNA; T(H) cells; allergy; asthma; eosinophils; inflammation; miR-155