title: MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during allergic airway inflammation in mice.
abstract: BACKGROUND
  Dendritic cells (DCs) are the professional antigen-presenting cells (APCs) in the lung. They are known to be key players in the induction and maintenance of allergic asthma by cross-linking innate and adaptive immune responses. MicroRNAs (miRNAs) are known to influence cell fate and function by translational suppression or induction of messenger RNA (mRNA) degradation. miR-155 has been shown to be a crucial regulator of the immune system. However, its function in the pathogenesis of allergic airway inflammation (AAI) is not completely elucidated yet.
  
  
  METHODS
  Wild type (WT) and miR-155-deficient (miR-155(-/-) ) mice were used in ovalbumin (OVA) and house dust mite (HDM) models of AAI. Adoptive transfer of sensitized DCs to the lungs, migration, and T-cell priming assays were used to investigate the functional relevance of miR-155 in DCs.
  
  
  RESULTS
  miR-155(-/-) mice showed reduced eosinophilic airway inflammation compared to WT mice in both models of AAI. Furthermore, miR-155(-/-) DCs showed limited Th2 priming capacity and failed to induce airway inflammation in allergen-exposed WT mice. miR-155 deficiency on DCs was also associated with impaired purinergic receptor signaling, as miR-155(-/-) DCs showed reduced chemotaxis and IL-1beta secretion upon stimulation with ATP, probably due to direct targeting of ectonucleoside triphosphate diphosphohydrolases (ENTPD) by miR-155.
  
  
  CONCLUSIONS
  miR-155 deficiency alleviates AAI by diminishing Th2 priming capacity and ATP-/P2R-induced activation of DCs in mice, suggesting this miRNA as a potential therapeutic target of AAI.
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zech
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: C K
authors.initials: CK
authors.lastname: Ayata
authors.affiliation: Department of Cardiology and Angiology, University Medical Centre, Freiburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Pankratz
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Baudiß
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Cicko
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku and National Institute of Health and Welfare, Turku, Finland.
authors.forename: G G
authors.initials: GG
authors.lastname: Yegutkin
authors.affiliation: Department of Cardiology and Angiology, University Medical Centre, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Grundmann
authors.affiliation: Department of Pneumology, University Medical Centre, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Idzko
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D010047:Ovalbumin / Q000276:immunology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D010047:Ovalbumin
keywords: P2R signaling; Th2 response; allergic airway inflammation; dendritic cells; microRNA-155