TGF-β suppresses β-catenin-dependent tolerogenic activation program in dendritic cells.
TGF-β suppresses β-catenin-dependent tolerogenic activation program in dendritic cells.
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DOI：
10.1371/journal.pone.0020099
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Boes M
中科院分区：
文献类型：
--
作者：
Vander Lugt B;Beck ZT;Fuhlbrigge RC;Hacohen N;Campbell JJ;Boes M
树突状细胞（DC）在外周免疫耐受中的关键作用机制尚未完全了解，尽管β-连环蛋白信号通路对此作用至关重要。DC中β-连环蛋白信号传导调节的分子细节尚不清楚。小鼠骨髓来源的DC（BMDC）簇的机械破坏激活DC，同时维持其致耐受性潜力，并且这种激活与β-连环蛋白信号传导相关，提供了一种有用的模型，用于探索DC中耐受相关的β-连环蛋白信号传导。在这份报告中，我们展示了新的分子特征的信号事件，控制DC激活响应机械刺激。非经典β-连环蛋白信号传导是这种致耐受性活化的重要组成部分，并由粘附分子（包括整联蛋白）调节。这种独特的β-连环蛋白依赖性信号传导途径在低水平下是组成性活性的，表明机械刺激不一定是诱导这种独特激活程序所必需的。我们还发现，免疫调节细胞因子TGF-β拮抗DC中的β-连环蛋白，从而选择性地抑制与致耐受性DC活化相关的信号传导，同时对LPS诱导的β-连环蛋白非依赖性免疫原性活化没有影响。这些发现为外周免疫耐受中DC功能的关键信号通路的调节提供了新的分子见解。
The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance.
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影响因子：
4.4
作者：
Sato, K;Kawasaki, H;Takahashi, TA
通讯作者：
Takahashi, TA
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
56.9
作者：
Huang, Q;Liu, DY;Hacohen, N
通讯作者：
Hacohen, N
影响因子：
7.5
作者：
Schwartz, Martin A.;DeSimone, Douglas W.
通讯作者：
DeSimone, Douglas W.
内源性转化生长因子β1在Langerhans细胞生物学中的作用：转化生长因子β1空小鼠的皮肤没有表皮Langerhans细胞。
DOI：
10.1084/jem.184.6.2417
发表时间：
1996-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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