Intestinal overexpression of interleukin (IL)-15 promotes tissue eosinophilia and goblet cell hyperplasia.

Abstract:

: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.

journal_name

Immunol Cell Biol

authors

Mussarat A,Manohar M,Verma AK,Upparahalli Venkateshaiah S,Zaidi A,Sanders NL,Zhu X,Mishra A

doi

10.1111/imcb.1036

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

273-283

issue

3

eissn

0818-9641

issn

1440-1711

journal_volume

96

pub_type

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