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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

Mirjam Kool UGent, Monique Willart UGent, Menno van Nimwegen, Ingrid Bergen, Philippe Pouliot UGent, J Christian Virchow, Neil Rogers, Fabiola Osorio, Caetano Reis E Sousa and Hamida Hammad UGent, et al. (2011) IMMUNITY. 34(4). p.527-540
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
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
journal title
IMMUNITY
Immunity
volume
34
issue
4
pages
527 - 540
Web of Science type
Article
Web of Science id
000290367300012
JCR category
IMMUNOLOGY
JCR impact factor
21.637 (2011)
JCR rank
4/138 (2011)
JCR quartile
1 (2011)
ISSN
1074-7613
DOI
10.1016/j.immuni.2011.03.015
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1234759
handle
http://hdl.handle.net/1854/LU-1234759
date created
2011-05-24 17:36:08
date last changed
2013-02-27 09:08:15
@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},
}

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, M., 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.