Tags

Type your tag names separated by a space and hit enter

Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders.
Immunology 2019; 157(2):110-121I

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.

Authors+Show Affiliations

Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University School of Medicine, New Orleans, LA, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30779114

Citation

Verma, Alok K., et al. "Intestinal Overexpression of IL-18 Promotes Eosinophils-mediated Allergic Disorders." Immunology, vol. 157, no. 2, 2019, pp. 110-121.
Verma AK, Kandikattu HK, Manohar M, et al. Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders. Immunology. 2019;157(2):110-121.
Verma, A. K., Kandikattu, H. K., Manohar, M., Shukla, A., Upparahalli Venkateshaiah, S., Zhu, X., & Mishra, A. (2019). Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders. Immunology, 157(2), pp. 110-121. doi:10.1111/imm.13051.
Verma AK, et al. Intestinal Overexpression of IL-18 Promotes Eosinophils-mediated Allergic Disorders. Immunology. 2019;157(2):110-121. PubMed PMID: 30779114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intestinal overexpression of IL-18 promotes eosinophils-mediated allergic disorders. AU - Verma,Alok K, AU - Kandikattu,Hemanth Kumar, AU - Manohar,Murli, AU - Shukla,Anshi, AU - Upparahalli Venkateshaiah,Sathisha, AU - Zhu,Xiang, AU - Mishra,Anil, Y1 - 2019/03/21/ PY - 2018/11/27/received PY - 2019/01/16/revised PY - 2019/02/11/accepted PY - 2020/06/01/pmc-release PY - 2019/2/20/pubmed PY - 2019/11/8/medline PY - 2019/2/20/entrez KW - EGID KW - Fabpi KW - IL-18 KW - eosinophils KW - eotaxin KW - peanut SP - 110 EP - 121 JF - Immunology JO - Immunology VL - 157 IS - 2 N2 - 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. SN - 1365-2567 UR - https://www.unboundmedicine.com/medline/citation/30779114/Intestinal_overexpression_of_IL-18_promotes_eosinophils-mediated_allergic_disorders L2 - https://doi.org/10.1111/imm.13051 DB - PRIME DP - Unbound Medicine ER -