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TSLP 增强辅助型 2 细胞的功能。

TSLP enhances the function of helper type 2 cells.

机构信息

Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.

出版信息

Eur J Immunol. 2011 Jul;41(7):1862-71. doi: 10.1002/eji.201041195. Epub 2011 Jun 7.

Abstract

The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic inflammation in both humans and mice. TSLP has been shown to promote a Th2-type response through upregulation of OX40L on dendritic cells, and through direct induction of IL-4 production in naïve CD4+ T cells. However, its direct effect on effector Th cells has not been extensively investigated. In this study, we show that the level of TSLP receptor (TSLPR) expression on mouse effector Th2 cells is higher than on Th1 and Th17 cells, and that TSLP induced proliferation of effector Th2, but not Th1 nor Th17 cells. TSLP also induced the phosphorylation of signal transducer and activator of transcription (Stat) 5, and expression of the anti-apoptotic factor Bcl-2 in Th2 cells. Finally, TSLP-mediated proliferation on Th2 cells was enhanced by TCR stimulation, through IL-4-mediated induction of TSLPR expression. Taken together, these results indicate that TSLP is involved in exacerbation of mouse Th2-mediated allergic inflammation in a Th2 environment through direct stimulation of Th2 effector cells.

摘要

细胞因子胸腺基质淋巴细胞生成素(TSLP)已被证实参与了人类和小鼠过敏炎症的发展和进展。TSLP 通过上调树突状细胞上的 OX40L,并通过直接诱导幼稚 CD4+T 细胞产生 IL-4,促进了 Th2 型反应。然而,其对效应 Th 细胞的直接作用尚未得到广泛研究。在这项研究中,我们表明,TSLP 受体(TSLPR)在小鼠效应 Th2 细胞上的表达水平高于 Th1 和 Th17 细胞,TSLP 诱导效应 Th2 细胞增殖,而不诱导 Th1 或 Th17 细胞增殖。TSLP 还诱导了 Th2 细胞中信号转导和转录激活因子(Stat)5 的磷酸化和抗凋亡因子 Bcl-2 的表达。最后,TSLP 通过 TCR 刺激增强了对 Th2 细胞的增殖作用,通过 IL-4 介导的 TSLPR 表达诱导。综上所述,这些结果表明,TSLP 通过直接刺激 Th2 效应细胞,参与了 Th2 环境中小鼠 Th2 介导的过敏炎症的恶化。

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