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Intestinal overexpression of interleukin ( IL )‐15 promotes tissue eosinophilia and goblet cell hyperplasia
Author(s) -
Mussarat Ahad,
Manohar Murli,
Verma Alok K,
Upparahalli Venkateshaiah Sathisha,
Zaidi Asifa,
Sanders Nathan L,
Zhu Xiang,
Mishra Anil
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.1036
Subject(s) - eosinophilia , jejunum , eosinophil , biology , small intestine , enterocyte , endocrinology , medicine , interleukin , immunology , interleukin 5 , cytokine , asthma
Interleukin ( IL )‐15 overexpression in eosinophilic gastrointestinal disorders is reported, but IL ‐15′s role in promoting eosinophilic gastroenteritis is largely unknown. Therefore, we generated enterocyte‐overexpressed IL ‐15 transgenic mice using Fabpi promoter. The Fabpi‐ IL ‐15 ( iIL ‐15) transgenic mice showed induced IL ‐15 levels in the jejunum with a marked increase in jejunum eosinophils. However, no induction of eosinophilia in the blood or any other gastrointestinal segment was observed. Eosinophilia in the jejunum villus was substantially higher in iIL ‐15 mice compared to wild‐type mice. In addition, goblet cell hyperplasia was also observed in the jejunum of iIL ‐15 mice. Furthermore, a significant correlation between induced IL ‐15 transcript and the IL ‐18 transcripts was observed. Therefore, to further understand the role of IL ‐18 in IL ‐15 mice associated gastrointestinal disorders, we generated iIL ‐15/ IL ‐18Rα −/− mice. Using these mice, we found that IL ‐18 has an important role in promoting IL ‐15‐induced eosinophilia. As intestinal IL ‐15 overexpression is reported in food intolerance, we examined OVA intolerance in iIL ‐15 mice. The OVA ‐sensitized and challenged iIL ‐15 mice experienced weight loss, diarrhea and eosinophilia in the jejunum. Taken together, our findings demonstrate that intestinal IL ‐15 overexpression induces IL ‐18‐dependent eosinophilia and immunoglobulins in the intestine that promotes food allergic responses.