Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish an Antitumor Environment in the Skin
Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish an Antitumor Environment in the Skin
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DOI：
10.1016/j.ccr.2012.08.017
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发表时间：
2012-10-16
期刊：
影响因子：
50.3
通讯作者：
Kopan, Raphael
中科院分区：
文献类型：
--
作者：
Demehri, Shadmehr;Turkoz, Ahu;Kopan, Raphael
胸腺基质淋巴细胞生成素（TSLP）是一种细胞因子，与诱导辅助性T细胞2（Th2）介导的过敏性炎症有关，最近已被证明可刺激实体瘤生长和转移。相反，对皮肤中Notch信号发生克隆性缺失的小鼠进行研究发现，屏障缺陷皮肤释放的高水平TSLP会引起严重炎症，导致Notch缺陷的表皮克隆逐渐消除，并对皮肤肿瘤发生具有抵抗力。我们发现CD4(+) T细胞对于介导TSLP的这些作用既是必需的也是足够的。重要的是，野生型皮肤中TSLP的过表达也会导致对肿瘤发生的抵抗力，证实了TSLP在皮肤中起到肿瘤抑制因子的作用。
Thymic Stromal Lymphopoietin (TSLP), a cytokine implicated in induction of T helper 2 (Th2)-mediated allergic inflammation, has recently been shown to stimulate solid tumor growth and metastasis. Conversely, studying mice with clonal loss of Notch signaling in their skin revealed that high levels of TSLP released by barrier-defective skin caused a severe inflammation, resulting in gradual elimination of Notch-deficient epidermal clones and resistance to skin tumorigenesis. We found CD4(+) T cells to be both required and sufficient to mediate these effects of TSLP. Importantly, TSLP overexpression in wild-type skin also caused resistance to tumorigenesis, confirming that TSLP functions as a tumor suppressor in the skin.