International Session（Workshop）2(JSGE・JGES・JSGCS)
Fri. November 3rd   9:30 - 12:00   Room 9: Portopia Hotel Main Building Kairaku 3
IS-W2-7_E
 Establishment of a novel innate immune-dependent mouse model of eosinophilic enteritis
Ryo Matsuoka
Department of Allergy and Clinical Immunology, National Research Institute for Children Health and Development
Background:
Eosinophilic enteritis (EoN), a type of eosinophilic gastrointestinal disease, is characterized by eosinophilic infiltration of the small intestine, but its pathogenesis remains largely unknown. Recently, administration of succinate to mice reportedly activated group 2 innate lymphoid cells (ILC2s) via secretion of IL-25 by intestinal tuft cells. ILC2s have been implicated in the induction of antigen-nonspecific type 2 inflammation. We hypothesized that long-term succinate administration would induce eosinophil infiltration of the gastrointestinal tract via the IL-25-ILC2 axis, and we tested that hypothesis in mice.
Methods:
Succinate or an equivalent molar amount of saline (vehicle) was added to the drinking water of 4-week-old C57BL/6 or transgenic mice for 21 days. Fecal characteristics, body weight change, eosinophil infiltration, and expression of eosinophil- and tuft cell-related genes and cytokines in the ileum were evaluated.
Results:
There was no diarrhea or bloody stool in either mouse group. However, the numbers of eosinophils and tuft cells in the ileum were significantly increased and weight gain was poor in the succinate group compared with the vehicle mice. Th2-related cytokines and tuft-cell-related gene levels were significantly elevated in the succinate group mice. Succinate-induced eosinophil infiltration was not seen in Skn1-a-/- (tuft-cell-deficient), IL-25-/-, Rag2-/-IL-2rg-/- or IL-5-/- mice.
Conclusion:
We newly established a tuft-cell-dependent innate-immune EoN mouse model. This novel model has the potential to help us elucidate the pathophysiology of human EoN.
Index Term 1: eosinophilic enteritis
Index Term 2: mouse model
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