过敏性哮喘中尿酸作为针对吸入性抗原和炎症介质的Th2细胞免疫的诱导子
2011/06/17
摘要
虽然已经清楚，尿酸晶体的沉积是痛风的主要病因，但尿酸在其他炎症性疾病中的作用尚不清楚。我们前期的研究发现，过敏原激发的哮喘患者和小鼠气道中存在尿酸释放，后者对吸入有害蛋白和临床相关的屋尘螨过敏原后出现的Th2细胞免疫、气道嗜酸性增加和支气管高反应是必须的。相反，给予尿酸晶体和蛋白抗原，能促进Th2细胞免疫和哮喘特征。尿酸的辅助作用不需要炎症小体(Nlrp3, Pycard)或白介素-1(Myd88, IL-1r)轴的参与。尿酸晶体通过脾脏酪氨酸激酶和PI3K δ信号活化树突状细胞而促进Th2细胞免疫。这些结果为Th2细胞的发育和尿酸作为过敏性炎症的一个必要启动子和放大器提供了证据。
（林江涛 审校）
Immunity. 2011 Apr 5. [Epub ahead of print]
An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma.
Kool M, Willart MA, van Nimwegen M, Bergen I, Pouliot P, Virchow JC, Rogers N, Osorio F, Reis E Souza C, Hammad H, Lambrecht BN.
Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University Ghent, Ghent 9000, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam 3015, The Netherlands; Department of Molecular Biomedical Research, VIB, Ghent 9052, Belgium.
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.
Immunity. 2011 Apr 5. [Epub ahead of print]
虽然已经清楚，尿酸晶体的沉积是痛风的主要病因，但尿酸在其他炎症性疾病中的作用尚不清楚。我们前期的研究发现，过敏原激发的哮喘患者和小鼠气道中存在尿酸释放，后者对吸入有害蛋白和临床相关的屋尘螨过敏原后出现的Th2细胞免疫、气道嗜酸性增加和支气管高反应是必须的。相反，给予尿酸晶体和蛋白抗原，能促进Th2细胞免疫和哮喘特征。尿酸的辅助作用不需要炎症小体(Nlrp3, Pycard)或白介素-1(Myd88, IL-1r)轴的参与。尿酸晶体通过脾脏酪氨酸激酶和PI3K δ信号活化树突状细胞而促进Th2细胞免疫。这些结果为Th2细胞的发育和尿酸作为过敏性炎症的一个必要启动子和放大器提供了证据。
（林江涛 审校）
Immunity. 2011 Apr 5. [Epub ahead of print]
An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma.
Kool M, Willart MA, van Nimwegen M, Bergen I, Pouliot P, Virchow JC, Rogers N, Osorio F, Reis E Souza C, Hammad H, Lambrecht BN.
Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University Ghent, Ghent 9000, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Centre, Rotterdam 3015, The Netherlands; Department of Molecular Biomedical Research, VIB, Ghent 9052, Belgium.
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.
Immunity. 2011 Apr 5. [Epub ahead of print]
上一篇：
产生自由基的骨髓源性调节性细胞：肺部炎症和气道高反应性的强效活化剂和抑制剂
下一篇：
肥大细胞导致的气道结构改变参与了严重哮喘的致病过程
