Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic esophagitis.
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作者：
嗜酸性食管炎（EoE）是一种以食管嗜酸性粒细胞增多为特征的食物过敏相关性炎症性疾病。EoE已变得越来越普遍，但目前的管理策略是非特定的。因此，迫切需要确定可以靶向治疗这种疾病的特定免疫途径。EoE与编码胸腺基质淋巴细胞生成素（TSLP）的基因多态性有关，TSLP是一种促进过敏性炎症的细胞因子，但TSLP如何促进EoE疾病的发病机制仍不清楚。在这里，我们描述了一种新的小鼠模型的EoE样疾病，独立开发的IgE，但依赖于TSLP引起的嗜碱性粒细胞。治疗性TSLP中和或嗜碱性粒细胞耗竭也改善了已建立的EoE样疾病。重要的是，在患有EoE的人类受试者中，我们观察到食管活检中TSLP水平升高和嗜碱性粒细胞反应增强，功能获得性TSLP多态性与嗜碱性粒细胞反应增加相关。总之，这些数据表明TSLP-嗜碱性粒细胞轴可以在治疗上靶向治疗EoE。
Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis remains unknown. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE but was dependent on TSLP-elicited basophils. Therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. Critically, in human subjects with EoE, we observed elevated TSLP levels and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses. Together, these data suggest that the TSLP-basophil axis could be therapeutically targeted to treat EoE.
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DOI：
10.4049/jimmunol.1200691
发表时间：
2012-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Giacomin PR;Siracusa MC;Walsh KP;Grencis RK;Kubo M;Comeau MR;Artis D
通讯作者：
Artis D
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Markowitz, JE;Spergel, JM;Liacouras, CA
通讯作者：
Liacouras, CA
影响因子：
4.4
作者：
Jessup, Heidi K.;Brewer, Avery W.;Comeau, Michael R.
通讯作者：
Comeau, Michael R.
影响因子：
5.5
作者：
Mishra, Anil;Schlotman, James;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.