Up-regulation of GITRL on dendritic cells by WGP improves anti-tumor immunity in murine Lewis lung carcinoma.
Up-regulation of GITRL on dendritic cells by WGP improves anti-tumor immunity in murine Lewis lung carcinoma.
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WGP 上调树突状细胞上的 GITRL 可改善小鼠 Lewis 肺癌的抗肿瘤免疫
DOI：
10.1371/journal.pone.0046936
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Tian J;Ma J;Ma K;Ma B;Tang X;Baidoo SE;Tong J;Yan J;Lu L;Xu H;Wang S
β-葡聚糖已被证明是一种有效的免疫调节剂，可刺激先天和适应性免疫反应，这有助于其抗肿瘤特性。然而，它们的作用机制仍然难以捉摸。糖皮质激素诱导的TNF受体配体（GITRL）是TNF超家族的一员，它与受体GITR结合，在效应T细胞和调节性T细胞上产生积极的共刺激信号，涉及广泛的T细胞功能，这对免疫反应的发展很重要。本研究发现，全β-葡聚糖颗粒（WGPs）可通过dectin-1受体激活树突状细胞（dc），提高dc上GITRL的表达。此外，我们证明了dc上GITRL的增加可以破坏Treg介导的抑制，并以GITR/GITRL依赖的方式增强效应T细胞的增殖。在肿瘤模型中，具有高水平GITRL的dc极有可能引发细胞毒性T淋巴细胞（CTL）反应，下调Treg细胞的抑制活性，从而导致肿瘤进展延迟。这些发现表明，颗粒β-葡聚糖可以作为一种免疫调节剂，刺激T细胞介导的强效适应性免疫，同时通过GITR/GITRL相互作用下调抑制免疫活性，从而形成更有效的肿瘤防御机制。
β-Glucans have been shown to function as a potent immunomodulator to stimulate innate and adaptive immune responses, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Glucocorticoid-induced TNF receptor ligand (GITRL), a member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells, generates a positive co-stimulatory signal implicated in a wide range of T cell functions, which is important for the development of immune responses. In this study, we found that whole β-glucan particles (WGPs) could activate dendritic cells (DCs) via dectin-1 receptor, and increase the expression of GITRL on DCs in vitro and in vivo. Furthermore, we demonstrated that the increased GITRL on DCs could impair the regulartory T cell (Treg)-mediated suppression and enhance effector T cell proliferation in a GITR/GITRL dependent way. In tumor models, DCs with high levels of GITRL were of great potential to prime cytotoxic T lymphocyte (CTL) responses and down-regulate the suppressive activity of Treg cells, thereby leading to the delayed tumor progression. These findings suggest that particulate β-glucans can be used as an immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate suppressive immune activity via GITR/GITRL interaction, leading to a more efficient defense mechanism against tumor development.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
影响因子：
8.7
作者：
Goodridge HS;Wolf AJ;Underhill DM
通讯作者：
Underhill DM
影响因子：
11.2
作者：
Bohn, JA;BeMiller, JN
通讯作者：
BeMiller, JN
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B