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An unexpected role for uric Acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma

(2011) IMMUNITY. 34(4). p.527-540
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
MONOSODIUM URATE CRYSTALS, AIRWAY INFLAMMATION, DENDRITIC CELLS, CD4(+) T-CELLS, XANTHINE-OXIDASE, HELPER TYPE-2 RESPONSE, INDUCED NEUTROPHIL ACTIVATION, NALP3 INFLAMMASOME, HOUSE-DUST MITE, ADAPTIVE IMMUNITY

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Citation

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Chicago
Kool, Mirjam, Monique Willart, Menno van Nimwegen, Ingrid Bergen, Philippe Pouliot, J Christian Virchow, Neil Rogers, et al. 2011. “An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma.” Immunity 34 (4): 527–540.
APA
Kool, Mirjam, Willart, M., van Nimwegen, M., Bergen, I., Pouliot, P., Virchow, J. C., Rogers, N., et al. (2011). An unexpected role for uric Acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. IMMUNITY, 34(4), 527–540.
Vancouver
1.
Kool M, Willart M, van Nimwegen M, Bergen I, Pouliot P, Virchow JC, et al. An unexpected role for uric Acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. IMMUNITY. 2011;34(4):527–40.
MLA
Kool, Mirjam, Monique Willart, Menno van Nimwegen, et al. “An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma.” IMMUNITY 34.4 (2011): 527–540. Print.
@article{1234759,
  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 \ensuremath{\delta} signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.},
  author       = {Kool, Mirjam and Willart, Monique and van Nimwegen, Menno and Bergen, Ingrid and Pouliot, Philippe and Virchow, J Christian and Rogers, Neil and Osorio, Fabiola and Reis E Sousa, Caetano and Hammad, Hamida and Lambrecht, Bart},
  issn         = {1074-7613},
  journal      = {IMMUNITY},
  keyword      = {MONOSODIUM URATE CRYSTALS,AIRWAY INFLAMMATION,DENDRITIC CELLS,CD4(+) T-CELLS,XANTHINE-OXIDASE,HELPER TYPE-2 RESPONSE,INDUCED NEUTROPHIL ACTIVATION,NALP3 INFLAMMASOME,HOUSE-DUST MITE,ADAPTIVE IMMUNITY},
  language     = {eng},
  number       = {4},
  pages        = {527--540},
  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},
  url          = {http://dx.doi.org/10.1016/j.immuni.2011.03.015},
  volume       = {34},
  year         = {2011},
}

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