title: An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma.
abstract: Although deposition of uric acid (UA) crystals is known as the cause of gout, it is unclear whether UA plays a role in other inflammatory diseases. We here have shown that UA is released in the airways of allergen-challenged asthmatic patients and mice, where it was necessary for mounting T helper 2 (Th2) cell immunity, airway eosinophilia, and bronchial hyperreactivity to inhaled harmless proteins and clinically relevant house dust mite allergen. Conversely, administration of UA crystals together with protein antigen was sufficient to promote Th2 cell immunity and features of asthma. The adjuvant effects of UA did not require the inflammasome (Nlrp3, Pycard) or the interleukin-1 (Myd88, IL-1r) axis. UA crystals promoted Th2 cell immunity by activating dendritic cells through spleen tyrosine kinase and PI3-kinase δ signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University Ghent, Ghent 9000, Belgium.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kool
authors.forename: Monique A M
authors.initials: MA
authors.lastname: Willart
authors.forename: Menno
authors.initials: M
authors.lastname: van Nimwegen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bergen
authors.forename: Philippe
authors.initials: P
authors.lastname: Pouliot
authors.forename: J Christian
authors.initials: JC
authors.lastname: Virchow
authors.forename: Neil
authors.initials: N
authors.lastname: Rogers
authors.forename: Fabiola
authors.initials: F
authors.lastname: Osorio
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis E Sousa
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D019570:Inhalation Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D014527:Uric Acid / Q000627:therapeutic use*
chemical_list: D000941:Antigens; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014527:Uric Acid; D019869:Phosphatidylinositol 3-Kinases