Vice President Research Group "Molecular Allergology", Paul-Ehrlich-Institut, Langen, Germany.
Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Sci Rep. 2019 Jul 3;9(1):9608. doi: 10.1038/s41598-019-45653-7.
Allergic enteritis (AE) is a gastrointestinal form of food allergy. This study aimed to elucidate cellular and molecular mechanisms of AE using a murine model. To induce AE, BALB/c wild type (WT) mice received intraperitoneal sensitization with ovalbumin (an egg white allergen) plus ALUM and feeding an egg white (EW) diet. Microarray analysis showed enhanced gene expression of CC chemokine receptor (CCR) 8 and its ligand, chemokine CC motif ligand (CCL) 1 in the inflamed jejunum. Histological and FACS analysis showed that CCR8 knock out (KO) mice exhibited slightly less inflammatory features, reduced eosinophil accumulation but accelerated neutrophil accumulation in the jejunums, when compared to WT mice. The concentrations of an eosinophil chemoattractant CCL11 (eotaxin-1), but not of IL-5, were reduced in intestinal homogenates of CCR8KO mice, suggesting an indirect involvement of CCR8 in eosinophil accumulation in AE sites by inducing CCL11 expression. The potential of CCR8 antagonists to treat allergic asthma has been discussed. However, our results suggest that CCR8 blockade may promote neutrophil accumulation in the inflamed intestinal tissues, and not be a suitable therapeutic target for AE, despite the potential to reduce eosinophil accumulation. This study advances our knowledge to establish effective anti-inflammatory strategies in AE treatment.
过敏性肠炎（AE）是一种食物过敏引起的胃肠道疾病。本研究旨在通过建立鼠模型来阐明 AE 的细胞和分子机制。为了诱导 AE，BALB/c 野生型（WT）小鼠经腹腔注射卵清蛋白（蛋清过敏原）和 ALUM 进行致敏，并给予蛋清饮食。微阵列分析显示，在炎症性空肠中，CC 趋化因子受体（CCR）8 及其配体趋化因子 CC 基序配体（CCL）1 的基因表达增强。组织学和 FACS 分析显示，与 WT 小鼠相比，CCR8 敲除（KO）小鼠的炎症特征略轻，嗜酸性粒细胞积聚减少，但中性粒细胞在空肠中的积聚加速。CCR8KO 小鼠肠匀浆中一种嗜酸性粒细胞趋化因子 CCL11（eotaxin-1）的浓度降低，而 IL-5 的浓度没有降低，这表明 CCR8 通过诱导 CCL11 表达间接参与 AE 部位嗜酸性粒细胞的积聚。已经讨论了 CCR8 拮抗剂治疗过敏性哮喘的潜力。然而，我们的结果表明，CCR8 阻断可能促进炎症性肠组织中中性粒细胞的积聚，而不是 AE 的合适治疗靶点，尽管有可能减少嗜酸性粒细胞的积聚。本研究为 AE 治疗中建立有效的抗炎策略提供了更多的知识。
