Rag2-deficient IL-1 Receptor Antagonist-deficient Mice Are a Novel Colitis Model in Which Innate Lymphoid Cell-derived IL-17 Is Involved in the Pathogenesis

被引：7

作者：

Akitsu, Aoi ^{[1
,2
,3
]}

Kakuta, Shigeru ^{[1
]}

Saijo, Shinobu ^{[1
]}

Iwakura, Yoichiro ^{[1
,2
,3
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Minato Ku, Tokyo 1088639, Japan

[2] Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Tokyo 1130032, Japan

[3] Tokyo Univ Sci, Res Inst Biomed Sci, Chiba 2780022, Japan

来源：

EXPERIMENTAL ANIMALS | 2014年 / 63卷 / 02期

关键词：

Colitis; IL-1; IL-17; innate lymphoid cells; regulatory Tcells; DELTA-T-CELLS; INTESTINAL INFLAMMATION; MONONUCLEAR-CELLS; MUCOSAL; INTERLEUKIN-1; IL-1-BETA; ARTHRITIS; ALPHA; TH17; TNF;

D O I：

10.1538/expanim.63.235

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

0906 ;

摘要：

Il1rn(-/-) mice spontaneously develop arthritis and aortitis by an autoimnnune mechanism and also develop dermatitis by an autoinflammatory mechanism. Here, we show that Rag2(-/-)Il1rn(-/-) mice develop spontaneous colitis with high mortality, making a contrast to the suppression of arthritis in these mice. Enhanced IL-17A expression in group 3 innate lymphoid cells (ILC3s) was observed in the colon of Rag2(-/-)Il1rn(-/-) mice. IL-17A-deficiency prolonged the survival of Rag2(-/-)Il1rn(-/-) mice, suggesting a pathogenic role of this cytokine in the development of intestinal inflammation. Although IL-17A-producing T cells were increased in Il1rn(-/-) mice, these mice did not develop colitis, because CD4(+)Foxp3(+) regulatory T cell population was also expanded. Thus, excess IL-1 signaling and IL-1-induced IL-17A from ILC3s cause colitis in Rag2(-/-)Il1rn(-/-) mice in which Treg cells are absent. These observations suggest that the balance between IL-17A-producing cells and Treg cells is important to keep the immune homeostasis of the colon.

引用

页码：235 / 246

页数：12

共 37 条

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