Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells.

Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells.
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DOI:
10.1007/s10620-009-0979-x
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发表时间:
2010-07
影响因子:
3.1
通讯作者:
Watanabe N
Watanabe N
中科院分区:
医学3区
文献类型:
--
作者:
Tanaka J;Saga K;Kido M;Nishiura H;Akamatsu T;Chiba T;Watanabe N

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胸腺基质淋巴生成素(TSLP)由肠上皮细胞(IECs)释放,在生理状态下,TSLP条件下的树突状细胞可能参与肠道免疫稳态和免疫球蛋白A(IgA)类的转换。相反,TSLP激活树突状细胞以诱导强大的T细胞增殖,并参与人类变态反应性疾病的炎性T辅助细胞(Th)2反应。然而,目前尚不清楚IECS在溃疡性结肠炎(UC)中如何调节TSLP的产生,这似乎涉及炎症性Th2反应。本研究的目的是研究IECS如何在溃疡性结肠炎中调节TSLP的产生。我们在这里显示,在UC患者的粘膜病变中,TSLP的表达增强,其中炎症Th2细胞因子的产生占主导地位。此外,使用人结肠上皮细胞系,我们证明了肿瘤坏死因子-α和白介素4(IL-4)联合诱导TSLP的表达,并且Toll样受体3配体或干扰素-γ进一步增强了Toll样受体3配体或干扰素-γ对TSLP的表达。综上所述,与人类变态反应性疾病一样,UC患者黏膜病变中的炎性Th2状态可能会触发IECS增加TSLP的表达,从而导致UC的恶化。
Thymic stromal lymphopoietin (TSLP) is released by intestinal epithelial cells (IECs), and TSLP-conditioned dendritic cells appear to be involved in immune homeostasis of intestine and immunoglobulin A (IgA) class-switching in the physiological condition. In contrast, TSLP activates dendritic cells to induce strong T-cell proliferation and is involved in inflammatory T helper (Th) 2 responses in human allergic diseases. However, it is not clear how TSLP production by IECs is regulated in ulcerative colitis (UC), which appears to involve inflammatory Th2 responses. The aim of this study is to examine how TSLP production by IECs is regulated in ulcerative colitis. We show here that expression of TSLP was enhanced in mucosal lesions from UC patients in which inflammatory Th2 cytokine production was predominant. In addition, using a human colonic epithelial cell line, we demonstrated that a combination of tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) induced TSLP expression and that TSLP expression by TNF-α + IL-4 was further enhanced by either Toll-like receptor 3 ligand or interferon (IFN)-γ. Taken together, as in human allergic diseases, an inflammatory Th2 condition in the mucosal lesions of UC patients may trigger increased TSLP expression by IECs, resulting in exacerbation of UC.
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