Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis

Interleukin-19 contributes as a protective factor in experimental Th2-mediated colitis
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DOI:
10.1007/s00210-016-1329-0
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发表时间:
2017-03-01
影响因子:
3.6
通讯作者:
Takeuchi, Tadayoshi
Takeuchi, Tadayoshi
中科院分区:
医学4区
文献类型:
--
作者:
Fujimoto, Yasuyuki;Azuma, Yasu-Taka;Takeuchi, Tadayoshi

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炎症性肠病由粘膜免疫系统的慢性失调和先天性和适应性免疫应答的异常激活引起。IL-19是IL-10家族的成员,IL-10在炎症性肠病中起重要作用。我们以前已经表明,IL-19基因敲除小鼠更容易患先天性结肠炎。接下来,我们询问IL-19是否有助于T细胞介导的结肠炎。在这里,我们研究了IL-19在Th 2细胞介导的结肠炎小鼠模型中的作用。使用由恶唑酮诱导的Th 2介导的结肠炎评估IL-19缺陷型小鼠中的炎症反应。通过分析体重减轻和结肠组织学来评价结肠炎。体外培养淋巴结细胞以测定细胞因子产生。IL-19基因敲除小鼠通过刺激炎性细胞向结肠的转运,以及通过增加IgE产生和循环嗜酸性粒细胞的数量,加重恶唑酮诱导的结肠炎。IL-19基因敲除小鼠后恶唑酮诱导的结肠炎症加剧伴随着IL-4和IL-9的产生增加,但淋巴结细胞中IL-5和IL-13的表达没有变化。IL-19在Th 2介导的结肠炎模型中起抗炎作用,表明IL-19可能代表用于减少结肠炎症的潜在治疗靶点。
Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. IL-19 is a member of the IL-10 family, and IL-10 plays an important role in inflammatory bowel disease. We have previously shown that IL-19 knockout mice are more susceptible to innate-mediated colitis. Next, we ask whether IL-19 contributes to T cells-mediated colitis. Here, we investigated the role of IL-19 in a mouse model of Th2 cell-mediated colitis. Inflammatory responses in IL-19-deficient mice were assessed using a Th2-mediated colitis induced by oxazolone. The colitis was evaluated by analyzing the body weight loss and histology of the colon. Lymph node cells were cultured in vitro to determine cytokine production. IL-19 knockout mice exacerbated oxazolone-induced colitis by stimulating the transport of inflammatory cells into the colon, and by increasing IgE production and the number of circulating eosinophil. The exacerbation of oxazolone-induced colonic inflammation following IL-19 knockout mice was accompanied by an increased production of IL-4 and IL-9, but no changes in the expression of IL-5 and IL-13 in lymph node cells. IL-19 plays an anti-inflammatory role in the Th2-mediated colitis model, suggesting that IL-19 may represent a potential therapeutic target for reducing colonic inflammation.