title: Inflammasome-IL-1-Th17 response in allergic lung inflammation.
abstract: Allergic asthma has increased dramatically in prevalence and severity over the last three decades. Both clinical and experimental data support an important role of Th2 cell response in the allergic response. Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid, activating the NLRP3 inflammasome complex and cleaving pro-IL-1β to mature IL-1β through caspase-1. The production of pro-IL-1β requires a toll-like receptor (TLR) 4 signal which is provided by the allergen. IL-1β creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung. Here, we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 cells plays a critical role in established asthma. Therefore, inflammasome activation leading to IL-1β production contributes to the control of allergic asthma by enhancing Th17 cell differentiation.
authors.affiliation: University of Orleans and Molecular Immunology and Embryology, CNRS UMR6218, Orleans, France.
authors.forename: Anne-Gaelle
authors.initials: AG
authors.lastname: Besnard
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Couillin
authors.forename: Zoming
authors.initials: Z
authors.lastname: Tan
authors.forename: Song Guo
authors.initials: SG
authors.lastname: Zheng
authors.forename: François
authors.initials: F
authors.lastname: Erard
authors.forename: Marc
authors.initials: M
authors.lastname: Le Bert
authors.forename: Valérie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D002454:Cell Differentiation; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014527:Uric Acid / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D020381:Interleukin-17; D053583:Interleukin-1beta; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051197:Toll-Like Receptor 4; D014527:Uric Acid; D000097043:Interleukin-22; C492716:Nlrp3 protein, mouse; C493487:Tlr4 protein, mouse