Prominent role of IFN-γ in patients with aspirin-exacerbated respiratory disease.
Prominent role of IFN-γ in patients with aspirin-exacerbated respiratory disease.
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DOI：
10.1016/j.jaci.2013.05.008
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Borish L
中科院分区：
文献类型：
--
作者：
Steinke JW;Liu L;Huyett P;Negri J;Payne SC;Borish L
Aspirin-exacerbated respiratory disease (AERD) is distinguished from aspirin tolerant asthma/chronic sinusitis in large part by an exuberant infiltration of eosinophils that are characterized by their over-expression of metabolic pathways that drive the constitutive and aspirin-induced secretion of cysteinyl leukotrienes (CysLTs). We defined the inflammatory milieu that in part drives CysLT overproduction and, in particular, the role of interferon (IFN)-γ in the differentiation of eosinophils. qPCR was performed for Th1 and Th2 signature cytokines on control, chronic hyperplastic eosinophilic sinusitis (CHES), and AERD tissue and their cellular source was determined. The influence of interferon (IFN)-γ on maturation, differentiation, and functionality of eosinophils derived from hematopoietic stem cells was determined. Gene expression analysis revealed that both aspirin tolerant and AERD tissue display a Th2 cytokine signature, however AERD was distinguished from CHES by the prominent expression of IFN-γ. Intracellular and immunohistochemical cytokine staining revealed that the major source of these cytokines were the eosinophils themselves. IFN-γ promoted the maturation of eosinophil progenitors as measured by increased mRNA and surface expression of CCR3 and Siglec-8. Additionally, IFN-γ increased expression of genes involved in leukotriene synthesis that led to increased secretion of cysteinyl leukotrienes. IFN-γ-matured eosinophil progenitors were also primed as demonstrated by their enhanced degranulation. High IFN-γ levels distinguish AERD from aspirin tolerant asthma and underlie the robust constitutive and aspirin-induced secretion of CysLTs that characterize this disorder.
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影响因子：
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作者：
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DOI：
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