Lei Liying, Zhang Yanlu, Yao Weiguo, Kaplan Mark H, Zhou Baohua
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Immunol. 2011 Feb 15;186(4):2254-61. doi: 10.4049/jimmunol.1002503. Epub 2011 Jan 17.
Thymic stromal lymphopoietin (TSLP) is an essential cytokine for the initiation and development of allergic inflammation. In this study, we have investigated the role of TSLP in the breakdown of immune tolerance and generation of inducible regulatory T cells (iTregs). Our results demonstrated that TSLP diverted airway tolerance against OVA to Th2 sensitization and inhibited the generation of OVA-specific iTregs. TSLP exerted a direct inhibitory effect on both human and mouse iTreg development in vitro. Low doses of TSLP were capable of inhibiting iTreg induction without significantly promoting Th2 development, indicating that these two functions of TSLP are separable. Moreover, the TSLP-mediated inhibition of iTreg generation was only partially dependent on IL-4 and Stat6, and was effective when TSLP was present for the first 24 h of T cell activation. These results define a novel role for TSLP in regulating the balance of airway tolerance and allergic inflammation.
胸腺基质淋巴细胞生成素（TSLP）是过敏性炎症起始和发展所必需的一种细胞因子。在本研究中，我们调查了TSLP在免疫耐受破坏及诱导性调节性T细胞（iTregs）生成中的作用。我们的结果表明，TSLP将针对卵清蛋白（OVA）的气道耐受转变为Th2致敏，并抑制OVA特异性iTregs的生成。TSLP在体外对人和小鼠iTreg的发育均发挥直接抑制作用。低剂量的TSLP能够抑制iTreg的诱导，而不会显著促进Th2的发育，这表明TSLP的这两种功能是可分离的。此外，TSLP介导的对iTreg生成的抑制仅部分依赖于白细胞介素-4（IL-4）和信号转导及转录激活因子6（Stat6），并且当TSLP在T细胞激活的最初24小时存在时是有效的。这些结果确定了TSLP在调节气道耐受和过敏性炎症平衡中的新作用。
