Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation.
Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation.
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DOI：
10.4049/jimmunol.1300199
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发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Shevach EM
中科院分区：
文献类型：
--
作者：
Edwards JP;Fujii H;Zhou AX;Creemers J;Unutmaz D;Shevach EM
GARP/LRRC32先前被定义为激活的人调节性t细胞（Tregs）的标记物，负责潜伏的TGF-β1的表面定位。我们发现在经TCR刺激激活的小鼠Tregs中也发现了GARP和潜伏的TGF-β1，但与人类Tregs不同的是，GARP在静息Tregs中也有低水平表达。在缺乏TCR信号的情况下，小鼠Tregs中暴露IL-2或IL-4可上调GARP的表达。GARP在胸腺内的Treg上低水平表达，来自胸腺的Treg前体在暴露于IL-2时同时表达GARP和Foxp3。GARP的表达不受TGF-β1和TGF-β1加载GARP的影响，也不受furin介导的前TGF-β1转化为潜伏TGF-β1的过程的影响。CD4+ T细胞中GARP的特异性缺失导致tgf -β1在活化的Tregs上缺乏表达。garp缺陷treg发育正常，外周组织中存在正常数量的treg，并且在体外是T常规细胞激活的完全有效抑制因子。表达GARP/latent-TGF-β1复合物的活化Tregs在外源IL-6存在时是Th17分化的有效诱导剂，在IL-2存在时是Treg的诱导剂。产生Th17的细胞和Treg的诱导均优先由Treg细胞表面表达potential - tgf -β1/GARP复合物诱导，而不是由分泌的potential - tgf -β1诱导。
GARP/LRRC32 has previously been defined as a marker of activated human regulatory T-cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation, but in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-β1 and TGF-β1 loading into GARP and is independent of furin-mediated processing of pro-TGF-β1 to latent TGF-β1. Specific deletion of GARP in CD4+ T cells results in lack of expression of latent-TGF-β1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of T conventional cells in vitro. Activated Tregs expressing GARP/latent-TGF-β1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17 producing cells and Treg is preferentially induced by Tregs expressing the latent-TGF-β1/GARP complex on their cell surface rather than by secreted latent-TGF-β1.
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影响因子：
64.8
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Pesu, Marko;Watford, Wendy T.;Wei, Lai;Xu, Lili;Fuss, Ivan;Strober, Warren;Andersson, John;Shevach, Ethan M.;Quezado, Martha;Bouladoux, Nicolas;Roebroek, Anton;Belkaid, Yasmine;Creemers, John;O'Shea, John J.
通讯作者：
O'Shea, John J.