Intestinal Overexpression of IL-18 Promotes Eosinophils-mediated Allergic Disorders

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2019 Feb 20

PMID 30779114

Citations 12

Authors

Alok K Verma

Hemanth Kumar Kandikattu

Murli Manohar

Anshi Shukla

Sathisha Upparahalli Venkateshaiah

Xiang Zhu

Anil Mishra

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Wang J, Zhan M, Zhai Y, Wang S, Gu F, Zhao Z Clin Exp Immunol. 2024; 217(1):31-44.

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Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis.

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Histamine Activates Human Eosinophils via HR and HR Predominantly in Atopic Dermatitis Patients.

Beyer L, Kabatas A, Mommert S, Stark H, Werfel T, Gutzmer R Int J Mol Sci. 2022; 23(18).

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Role of IL-18-transformed CD274-expressing eosinophils in promoting airway obstruction in experimental asthma.

Mishra A, Majid D, Kandikattu H, Yadavalli C, Upparahalli Venkateshaiah S Allergy. 2021; 77(4):1165-1179.

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Macrophages-induced IL-18-mediated eosinophilia promotes characteristics of pancreatic malignancy.

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