Macrophage migration inhibitory factor promotes eosinophil accumulation and tissue remodeling in eosinophilic esophagitis.
Macrophage migration inhibitory factor promotes eosinophil accumulation and tissue remodeling in eosinophilic esophagitis.
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DOI：
10.1038/mi.2015.6
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发表时间：
2015-09
影响因子：
8
通讯作者：
Bozza MT
中科院分区：
文献类型：
--
作者：
de Souza HS;Tortori CA;Lintomen L;Figueiredo RT;Bernardazzi C;Leng L;Bucala R;Madi K;Buongusto F;Elia CC;Castelo-Branco MT;Bozza MT
巨噬细胞移动抑制因子（MIF）参与嗜酸性粒细胞生物学和2型炎症，导致过敏性和蠕虫病。我们假设MIF参与嗜酸性食管炎（EoE）的发病机制，EoE是一种以食管嗜酸性炎症为特征的过敏性疾病。与胃食管反流病和对照患者相比，MIF在EoE患者的食管粘膜中高度表达，其中它主要与嗜酸性粒细胞共定位。在体外，重组MIF促进人嗜酸性粒细胞的趋化性，而MIF拮抗剂和CXCR4拮抗剂，AMD 3100，逆转这种作用。在由卵清蛋白诱导的EoE模型中，与野生型小鼠相比，Mif缺陷型小鼠具有减少的炎症和胶原沉积。重要的是，在激发阶段用抗MIF或AMD 3100处理野生型小鼠可防止嗜酸性粒细胞蓄积和组织重塑。相反，重组MIF促进过敏小鼠组织嗜酸性粒细胞炎症。总之，这些结果暗示MIF在食管炎症的发病机制，并建议，针对MIF可能代表一种新的治疗EoE。
Macrophage migration inhibitory factor (MIF) is involved in eosinophil biology and in Type 2 inflammation, contributing to allergic and helminthic diseases. We hypothesized that MIF participates in the pathogenesis of eosinophilic esophagitis (EoE), an allergic condition characterized by esophageal eosinophilic inflammation. MIF is highly expressed in esophageal mucosa of patients with EoE, compared to gastro-esophageal reflux disease and control patients, where it co-localizes predominantly with eosinophils. In vitro, recombinant MIF promotes human eosinophil chemotaxis, while MIF antagonist and CXCR4 antagonist, AMD3100, revert this effect. In a model of EoE induced by ovalbumin, Mif deficient mice have reduced inflammation and collagen deposition compared to wild type mice. Importantly, treatment of wild type mice with anti-MIF or with AMD3100 during the challenge phase prevents accumulation of eosinophils and tissue remodeling. Conversely, recombinant MIF promoted tissue eosinophil inflammation in allergic mice. Together, these results implicate MIF in the pathogenesis of esophageal inflammation and suggest that targeting MIF might represent a novel therapy for EoE.