An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma
Authors list
Mirjam Kool Monique AM Willart Menno van Nimwegen Ingrid Bergen Philippe Pouliot J Christian Virchow Neil Rogers Fabiola Osorio Caetano Reis e Sousa Hamida Hammad Bart N LambrechtAbstract
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.
Full text links
Publisher website (DOI) 10.1016/j.immuni.2011.03.015
Europe PubMed Central 21474346
Pubmed 21474346
Keywords
Type of publication