title: MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation.
abstract: BACKGROUND
  Allergic airway inflammation is triggered by allergen exposure through several steps including release of IL-33, which promotes cytokine (IL-5, IL-13) production by type 2 innate lymphoid cells (ILC2s). MicroRNA (miR)-155 has recently been described to regulate adaptive responses in allergic inflammation. However, the role of miR-155 in the regulation of ILC2s remains unexplored.
  
  
  OBJECTIVE
  We sought to elucidate the contribution of miR-155 in ILC2 expansion using experimental murine models of allergic airway inflammation.
  
  
  METHODS
  To determine the role of miR-155 in the regulation of ILC2s in allergic airway inflammation, miR-155 deficient (miR-155-/-) and wild-type (WT) mice were subjected to acute or chronic allergen-induced inflammation or treated with recombinant IL-33.
  
  
  RESULTS
  miR-155 was 10-fold upregulated in WT-derived ILC2s in response to IL-33. Furthermore, miR-155-/-mice demonstrated impaired lung IL-33 levels in response to allergen challenge and the number of ILC2s was significantly reduced in allergen-challenged miR-155-/-mice compared with WT mice. Exogenous IL-33 treatment revealed that miR-155 is needed for IL-33-induced ILC2 expansion and eosinophilic airway inflammation. Indeed, ILC2s from IL-33-challenged miR-155-/-lungs exhibited impaired proliferation, GATA-3 expression, and IL-13 production as compared with IL-33-challenged WT ILC2s.
  
  
  CONCLUSIONS
  Our findings for the first time demonstrate that ILC2s and IL-33 signaling are regulated by miR-155 in allergic airway inflammation.
authors: Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors: Kristina
authors: K
authors: Johansson
authors: Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors: Carina
authors: C
authors: Malmhäll
authors: Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors: Patricia
authors: P
authors: Ramos-Ramírez
authors: Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: madeleine.radinger@gu.se.
authors: Madeleine
authors: M
authors: Rådinger
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000276:immunology; D007113:Immunity, Innate; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology*; D000067596:Interleukin-33 / Q000276:immunology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction
chemical_list: D000485:Allergens; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C556694:Icos protein, mouse; C506535:Il33 protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D010047:Ovalbumin; D003094:Collagen
keywords: IL-13; IL-33; ILC2; allergy; asthma; eosinophils; miR-155