GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.
GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.
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DOI：
10.1371/journal.pone.0076186
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lucas S
中科院分区：
文献类型：
--
作者：
Gauthy E;Cuende J;Stockis J;Huygens C;Lethé B;Collet JF;Bommer G;Coulie PG;Lucas S
GARP是一种跨膜蛋白，存在于刺激的人调节性T淋巴细胞（Tlymphocyte，Tlymphocyte）上，但不存在于其他T淋巴细胞（Th细胞）上。它在Treg表面呈现TGF-β1的潜伏形式。我们在此报道GARP有利于TGF-β1前体的切割，并增加分泌的潜伏TGF-β1的量。天然表达GARP的受刺激的TGF 3和用GARP转染的Th细胞分泌一种以前未知形式的潜伏性TGF-β1，其与GARP二硫键连接。这些GARP/TGF-β1复合物可能从T细胞表面脱落。在转染的293细胞中未观察到GARP/TGF-β1复合物的分泌，因此可能仅限于T细胞谱系。我们的结论是，在刺激的人TCRP中，GARP不仅在细胞表面显示潜伏的TGF-β1，而且通过形成可溶性二硫键连接的复合物来增加其分泌。此外，我们鉴定了六种在Treg中表达水平低于Th克隆的microRNA（miRNA），并且它们靶向GARP 3' UTR的短区域。在转染的Th细胞中，该区域的存在降低了GARP水平、pro-TGF-β1的切割和潜伏TGF-β1的分泌。
GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1. Stimulated Tregs, which naturally express GARP, and Th cells transfected with GARP secrete a previously unknown form of latent TGF-β1 that is disulfide-linked to GARP. These GARP/TGF-β1 complexes are possibly shed from the T cell surface. Secretion of GARP/TGF-β1 complexes was not observed with transfected 293 cells and may thus be restricted to the T cell lineage. We conclude that in stimulated human Tregs, GARP not only displays latent TGF-β1 at the cell surface, but also increases its secretion by forming soluble disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs) that are expressed at lower levels in Treg than in Th clones and that target a short region of the GARP 3’ UTR. In transfected Th cells, the presence of this region decreased GARP levels, cleavage of pro-TGF-β1, and secretion of latent TGF-β1.
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DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
Merkenschlager M
影响因子：
4.8
作者：
DUBOIS, CM;LAPRISE, MH;LEDUC, R
通讯作者：
LEDUC, R
影响因子：
4.4
作者：
Klein, Matthias;Vaeth, Martin;Becker, Christian
通讯作者：
Becker, Christian
影响因子：
4.4
作者：
Nakamura, K;Kitani, A;Strober, W
通讯作者：
Strober, W
影响因子：
32.4
作者：
Lu, Li-Fan;Thai, To-Ha;Calado, Dinis Pedro;Chaudhry, Ashutosh;Kubo, Masato;Tanaka, Kentaro;Loeb, Gabriel B.;Lee, Hana;Yoshimura, Akihiko;Rajewsky, Klaus;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.