Intestinal overexpression of IL IL ‐18 promotes eosinophils‐mediated allergic disorders

摘要

Summary Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in?vitro that interleukin ( IL )‐18 matures and transforms IL ‐5‐generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL ‐18 in promoting eosinophil‐associated intestinal disorders, we generated enterocyte IL ‐18‐overexpressing mice using the rat intestinal fatty acid‐binding promoter (Fabpi) and analysed tissue IL ‐18 overexpression and eosinophilia by performing real‐time polymerase chain reaction, Enzyme‐Linked Immunosorbent Assay and anti‐major basic protein immunostaining. Herein we show that Fabpi‐ IL ‐18 mice display highly induced IL ‐18 mRNA and protein in the jejunum. IL ‐18 overexpression in enterocytes promotes marked increases of eosinophils in the blood and jejunum. Our analysis shows IL ‐18 overexpression in the jejunum induces a specific population of CD 101 +? CD 274 + tissue eosinophils. Additionally, we observed comparable tissue eosinophilia in IL ‐13‐deficient‐Fabpi‐ IL ‐18 mice, and reduced numbers of tissue eosinophils in eotaxin‐deficient‐Fabpi‐ IL ‐18 and IL ‐5‐deficient‐Fabpi‐ IL ‐18 mice compared with Fabpi‐ IL ‐18 transgenic mice. Notably, jejunum eosinophilia in IL ‐5‐deficient‐Fabpi‐ IL‐ 18 mice is significantly induced compared with wild‐type mice, which indicates the direct role of induced IL ‐18 in the tissue accumulation of eosinophils and mast cells. Furthermore, we also found that overexpression of IL ‐18 in the intestine promotes eosinophil‐associated peanut‐induced allergic responses in mice. Taken together, we provide direct in?vivo evidence that induced expression of IL ‐18 in the enterocytes promotes eotaxin‐1, IL ‐5 and IL ‐13 independent intestinal eosinophilia, which signifies the clinical relevance of induced IL ‐18 in eosinophil‐associated gastrointestinal disorders (EGIDs) to food allergens.