title: NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant.
abstract: BACKGROUND
  Inflammasome activation with the production of IL-1β received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway.
  
  
  METHODS
  Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1β or IL-1α. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo.
  
  
  RESULTS
  Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1β is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1β-, and IL-1α-deficient mice.
  
  
  CONCLUSIONS
  NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response.
authors: Université d'Orléans and CNRS, Molecular Immunology and Embryology (IEM), Orléans, France.
authors: A-G
authors: AG
authors: Besnard
authors: N
authors: N
authors: Guillou
authors: J
authors: J
authors: Tschopp
authors: F
authors: F
authors: Erard
authors: I
authors: I
authors: Couillin
authors: Y
authors: Y
authors: Iwakura
authors: V
authors: V
authors: Quesniaux
authors: B
authors: B
authors: Ryffel
authors: D
authors: D
authors: Togbe
mesh_terms: D000276:Adjuvants, Immunologic; D000535:Aluminum; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis; D053583:Interleukin-1beta; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010047:Ovalbumin; D011014:Pneumonia; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017472:Receptors, Interleukin-1; D010047:Ovalbumin; D000535:Aluminum