Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders.
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 CD101+  CD274+ 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.
['Verma|Alok K|AK|', 'Kandikattu|Hemanth Kumar|HK|', 'Manohar|Murli|M|', 'Shukla|Anshi|A|', 'Upparahalli Venkateshaiah|Sathisha|S|', 'Zhu|Xiang|X|', 'Mishra|Anil|A|0000-0003-4266-4684']
D000818:Animals D015703:Antigens, CD D060890:B7-H1 Antigen D054413:Chemokine CCL11 D020895:Enterocytes D004804:Eosinophils D006801:Humans D018793:Interleukin-13 D020382:Interleukin-18 D015848:Interleukin-5 D007583:Jejunum D008407:Mast Cells D051379:Mice D008822:Mice, Transgenic D021183:Peanut Hypersensitivity D051381:Rats
IL-18 eosinophils Fabpi EGID eotaxin peanut