Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates experimental autoimmune encephalomyelitis.
Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.jaut.2008.12.004
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发表时间：
2009-03
影响因子：
12.8
通讯作者：
Weiner HL
中科院分区：
文献类型：
--
作者：
Yang K;Vega JL;Hadzipasic M;Schatzmann Peron JP;Zhu B;Carrier Y;Masli S;Rizzo LV;Weiner HL
转化生长因子β（TGF-β）在诱导Treg和分泌IL-17的T细胞（Th 17）分化中起作用，所述T细胞驱动实验性自身免疫性脑脊髓炎（EAE）中的炎症。我们研究了EAE中血小板反应蛋白-1（TSP-1）依赖性TGF-β激活在脑炎性Th 17应答产生中的作用。经髓鞘少突胶质细胞糖蛋白肽（MOG 35 -55）免疫后，TSP-1缺陷型（TSP-1 null）小鼠和TSP-1缺陷型（2D 2·TSP-1 null）MOG 35 -55 TCR转基因小鼠表现出减弱的EAE形式，并且分泌较低水平的IL-17。体外活化的2D 2·TSP-1 null T细胞的连续转移诱导了较轻形式的EAE，与受体小鼠中TSP-1的表达无关。此外，体外研究表明，抗CD 3/抗CD 28预活化的CD 4 + T细胞以TSP-1依赖性方式瞬时上调潜伏TGF-β，并且这种潜伏TGF-β的活化是Th 17细胞分化所需的。这些结果表明，TSP-1通过其激活潜在TGF-β的能力参与Th 17细胞的分化，并增强EAE中的炎症反应。
Transforming growth factor β (TGF-β) plays a role both in the induction of Treg and in the differentiation of the IL-17-secreting T cells (Th17) which drive inflammation in experimental autoimmune encephalomyelitis (EAE). We investigated the role that thrombospondin-1 (TSP-1) dependent activation of TGF-β played in the generation of an encephalitic Th17 response in EAE. Upon immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55), TSP-1 deficient (TSP-1null) mice and MOG35-55 TCR transgenic mice that lack of TSP-1 (2D2·TSP-1null) exhibited an attenuated form of EAE, and secreted lower levels of IL-17. Adoptive transfer of in vitro activated 2D2·TSP-1null T cells induced a milder form of EAE, independent of TSP-1 expression in the recipient mice. Furthermore, in vitro studies demonstrated that anti-CD3/anti-CD28 pre-activated CD4+ T cells transiently upregulate latent TGF-β in a TSP-1 dependent way, and such activation of latent TGF-β is required for the differentiation of Th17 cells. These results demonstrate that TSP-1 participates the differentiation of Th17 cells through its ability to activate latent TGF-β, and enhances the inflammatory response in EAE.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5.6
作者：
LAWRENCE, DA;PIRCHER, R;JULLIEN, P
通讯作者：
JULLIEN, P
影响因子：
15.9
作者：
Bornstein, P
通讯作者：
Bornstein, P
影响因子：
32.4
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
6
作者：
Bullard, Daniel C.;Hu, Xianzhen;Barnum, Scott R.
通讯作者：
Barnum, Scott R.