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

摘要

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 that interleukin ( )‐18 matures and transforms ‐5‐generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of ‐18 in promoting eosinophil‐associated intestinal disorders, we generated enterocyte ‐18‐overexpressing mice using the rat intestinal fatty acid‐binding promoter (Fabpi) and analysed tissue ‐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‐ ‐18 mice display highly induced ‐18 and protein in the jejunum. ‐18 overexpression in enterocytes promotes marked increases of eosinophils in the blood and jejunum. Our analysis shows ‐18 overexpression in the jejunum induces a specific population of 101 274 tissue eosinophils. Additionally, we observed comparable tissue eosinophilia in ‐13‐deficient‐Fabpi‐ ‐18 mice, and reduced numbers of tissue eosinophils in eotaxin‐deficient‐Fabpi‐ ‐18 and ‐5‐deficient‐Fabpi‐ ‐18 mice compared with Fabpi‐ ‐18 transgenic mice. Notably, jejunum eosinophilia in ‐5‐deficient‐Fabpi‐ 18 mice is significantly induced compared with wild‐type mice, which indicates the direct role of induced ‐18 in the tissue accumulation of eosinophils and mast cells. Furthermore, we also found that overexpression of ‐18 in the intestine promotes eosinophil‐associated peanut‐induced allergic responses in mice. Taken together, we provide direct evidence that induced expression of ‐18 in the enterocytes promotes eotaxin‐1, ‐5 and ‐13 independent intestinal eosinophilia, which signifies the clinical relevance of induced ‐18 in eosinophil‐associated gastrointestinal disorders (EGIDs) to food allergens.