Department of Immunology, University of Washington, Seattle, WA 98195, USA.
J Immunol. 2010 Mar 15;184(6):2974-84. doi: 10.4049/jimmunol.0803478. Epub 2010 Feb 19.
Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. In this study, we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity in mice. TSLP is required for the development of Th2-type contact hypersensitivity induced by the hapten FITC in combination with the sensitizing agent dibutyl phthalate. TSLPR-deficient mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR-deficient mice is likely due to decreased frequency and reduced T cell stimulatory function of skin-derived Ag-bearing FITC(+)CD11c(+) dendritic cells in draining lymph nodes following FITC sensitization. These data suggest that skin-derived dendritic cells are direct or indirect targets of TSLP in the development of type 2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naive allergen-specific T cells.
胸腺基质淋巴细胞生成素 (TSLP) 是一种与白细胞介素 7 相关的细胞因子,由上皮细胞产生,与特应性皮炎和哮喘有关;然而,TSLP 如何塑造导致这些过敏疾病的适应性免疫反应仍不清楚。在这项研究中,我们证明了 TSLP 在小鼠接触性超敏反应的 Th2 模型中的作用。在与敏化剂邻苯二甲酸二丁酯联合使用半抗原 FITC 诱导的 Th2 型接触性超敏反应中,TSLP 是必需的。TSLPR 缺陷小鼠表现出明显的反应降低,包括 FITC 敏化和挑战后局部嗜酸性粒细胞浸润、Th2 细胞因子产生和血清 IgE 水平明显降低。TSLPR 缺陷小鼠的反应降低可能是由于 FITC 敏化后引流淋巴结中皮肤来源的 Ag 结合 FITC(+)CD11c(+)树突状细胞的频率降低和 T 细胞刺激功能降低。这些数据表明,皮肤来源的树突状细胞是 TSLP 在皮肤中诱导 2 型免疫反应中的直接或间接靶标,TSLP 驱动其成熟、在皮肤引流淋巴结中的积累以及诱导幼稚过敏原特异性 T 细胞增殖的能力。
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