Transgenic expression of IL-33 activates CD8+ T cells and NK cells and inhibits tumor growth and metastasis in mice
Transgenic expression of IL-33 activates CD8+ T cells and NK cells and inhibits tumor growth and metastasis in mice
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DOI：
10.1016/j.canlet.2013.03.002
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发表时间：
2013-07-28
期刊：
影响因子：
9.7
通讯作者：
Zhang, Lianfeng
中科院分区：
文献类型：
--
作者：
Gao, Kun;Li, Xiaoying;Zhang, Lianfeng
IL-33是免疫调节中的多功能细胞因子，其激活Th 1细胞、Th 2细胞、CD 8（+）T细胞和NK细胞。我们的研究表明，IL-33的转基因表达减弱了B16黑色素瘤和刘易斯肺癌（LLC）转移模型中的肿瘤转移。IL-33的转基因表达可显著增加荷瘤小鼠体内CD 8 + T细胞和NK细胞的比例、杀伤活性及其向肿瘤组织的浸润。重组IL-33还能增强CD 8 + T细胞和NK细胞的体外杀伤活性。此外，使用抗CD 8或抗去唾液酸GM 1抗体去除CD 8（+）T细胞和NK细胞消除了IL-33介导的肺转移抑制。此外，IL-33刺激NF-κ B B的活化并增加CD 69表达，这是CD 8（+）T细胞和NK细胞中两种细胞亚群活化形式的标志物。我们的研究结果表明，IL-33刺激NF-κ B B信号，促进CD 8（+）T细胞和NK细胞的增殖、活化和浸润，从而抑制B16黑色素瘤和LLC小鼠模型的肺转移。(C)2013爱思唯尔爱尔兰有限公司版权所有。
IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8(+) T cells and NK cells. Our study showed that transgenic expression of IL-33 attenuated tumor metastasis in the B16 melanoma and Lewis lung carcinoma (LLC) metastatic models. The percentages and cytotoxicity of CD8(+) T cells and NK cells and their infiltration into the tumor tissues were significantly increased by the transgenic expression of IL-33 in tumor-bearing mice. Treatment with recombinant IL-33 could also increase the cytotoxicity of CD8(+) T cells and NK cells in vitro. In addition, depletion of CD8(+)T cells and NK cells using anti-CD8 or anti-asialo GM1 antibody abolished the pulmonary metastasis inhibition mediated by IL-33. Furthermore, IL-33 stimulated the activation of NF-kappa B and increased CD69 expression, which is a marker of the activated form of the two cell subsets, in CD8(+) T cells and NK cells. Our results suggest that IL-33 stimulated NF-kappa B signaling and promoted the proliferation, activation and infiltration of CD8(+) T cells and NK cells, which resulted in the inhibition of pulmonary metastasis in B16 melanoma and LLC mice models. (C) 2013 Elsevier Ireland Ltd. All rights reserved.