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; MAM Willart; Menno van Nimwegen; Ingrid Bergen; P Pouliot; JC Virchow; N Rogers; F Osorio; C Reis e Sousa; H (Hamida) Hammad; Bart Lambrecht

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, MAM Willart, Menno van Nimwegen, Ingrid Bergen, P Pouliot, JC Virchow, N Rogers, F Osorio, C Reis e Sousa, H (Hamida) Hammad, Bart Lambrecht

Pulmonary Medicine

Research output: Contribution to journal › Article › Academic › peer-review

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 (NIrp3, 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 delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.

Original language	Undefined/Unknown
Pages (from-to)	527-540
Number of pages	14
Journal	Immunity
Volume	34
Issue number	4
Publication status	Published - 2011

Research programs

EMC MM-04-42-02

Cite this

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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 (NIrp3, 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 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 = "Mirjam Kool and MAM Willart and {van Nimwegen}, Menno and Ingrid Bergen and P Pouliot and JC Virchow and N Rogers and F Osorio and {Reis e Sousa}, C and Hammad, {H (Hamida)} and Bart Lambrecht",

year = "2011",

language = "Undefined/Unknown",

volume = "34",

pages = "527--540",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "4",

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TY - JOUR

T1 - An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma

AU - Kool, Mirjam

AU - Willart, MAM

AU - van Nimwegen, Menno

AU - Bergen, Ingrid

AU - Pouliot, P

AU - Virchow, JC

AU - Rogers, N

AU - Osorio, F

AU - Reis e Sousa, C

AU - Hammad, H (Hamida)

AU - Lambrecht, Bart

PY - 2011

Y1 - 2011

N2 - 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 (NIrp3, 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 delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.

AB - 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 (NIrp3, 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 delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.

M3 - Article

SN - 1074-7613

VL - 34

SP - 527

EP - 540

JO - Immunity

JF - Immunity

IS - 4

ER -