title: Effect of IL-37 on Allergic Airway Inflammation.
abstract: BACKGROUND
  The new cytokine IL-37 has been described as a negative regulator of innate immunity. It reduces activation of dendritic cells and the production of proinflammatory mediators in murine and human immune cells. Although recent results from the CLARA childhood asthma cohort suggested an impact of IL-37 on human asthma pathogenesis, the receptor for IL-37 and its implication in adaptive immune responses have not been determined.
  
  
  OBJECTIVE
  This study aimed to clarify whether IL-37 also provides antiinflammatory effects on adaptive immune responses and through which receptor it exerts its effects.
  
  
  METHODS
  IL-37 levels in supernatants of restimulated peripheral blood mononuclear cells isolated from children with asthma and healthy children were determined. Mice (wild-type, IL-18Rα(-/-), and SIGIRR/IL-1R8(-/-)) were sensitized to ovalbumin (OVA) and challenged with OVA aerosol to induce acute allergic experimental asthma, and IL-37 was applied intranasally during OVA challenge. Airway hyperresponsiveness was determined. A cytometric bead array was used to assess cytokine levels in bronchoalveolar lavage fluid. Epithelial mucus was quantified on the basis of lung sections stained with periodic acid-Schiff reagent, using the newCAST microscope system.
  
  
  RESULTS
  Human peripheral blood mononuclear cells of subjects with allergic asthma produce less IL-37 compared with healthy control subjects. In mice, intranasal administration of IL-37 dampened allergic airway inflammation as well as proinflammatory cytokine production, mucus hyperproduction, and airway hyperresponsiveness. However, the antiinflammatory effects of IL-37 were completely abolished in mice deficient for IL-18Rα or SIGIRR/IL-1R8.
  
  
  CONCLUSIONS
  This study demonstrates that IL-37 reduces allergic airway inflammation directed by type 2 helper T cells and the hallmarks of experimental asthma in mice, suggesting that IL-37 may be critical for asthma pathogenesis in particular and may have an impact on adaptive immunity in general. Furthermore, these data suggest a mode of action of IL-37 that involves binding to IL-18Rα and subsequent heterodimerization with or activation of SIGIRR/IL-1R8. Therefore, IL-37 or its receptors could be potential targets for asthma intervention.
authors.affiliation: 1 Division of Asthma Mouse Models and.
authors.forename: Lars
authors.initials: L
authors.lastname: Lunding
authors.affiliation: 2 Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, Borstel; and.
authors.forename: Sina
authors.initials: S
authors.lastname: Webering
authors.affiliation: 2 Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, Borstel; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Vock
authors.affiliation: 1 Division of Asthma Mouse Models and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schröder
authors.affiliation: 3 Department of Pulmonary and Allergy, Ludwig Maximilian University Munich, Comprehensive Pneumology Center-Munich, Member of the German Center for Lung Research, University Children's Hospital Munich, Munich, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Raedler
authors.affiliation: 3 Department of Pulmonary and Allergy, Ludwig Maximilian University Munich, Comprehensive Pneumology Center-Munich, Member of the German Center for Lung Research, University Children's Hospital Munich, Munich, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
authors.affiliation: 2 Division of Experimental Pneumology, Priority Area Asthma and Allergy, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research, Borstel; and.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fehrenbach
authors.affiliation: 1 Division of Asthma Mouse Models and.
authors.forename: Michael
authors.initials: M
authors.lastname: Wegmann