Transcription factor c-Rel is indispensable for generation of thymic but not of peripheral Foxp3(+) regulatory T cells.
Transcription factor c-Rel is indispensable for generation of thymic but not of peripheral Foxp3(+) regulatory T cells.
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DOI：
10.18632/oncotarget.17079
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Visekruna A
中科院分区：
文献类型：
--
作者：
Luu M;Jenike E;Vachharajani N;Visekruna A
转录因子c-rel已被证明对调节性T细胞(Tregs)的发育至关重要。最近的研究报道，转录因子Helios在Foxp3+Tregs中的表达与这些细胞(TTregs)的胸腺来源有关。值得注意的是，我们发现只有Helios+Foxp3+Treg细胞在c-rel缺陷小鼠中显著减少。与tTreg发育缺陷相反，我们观察到在REL−/−小鼠急性结肠炎诱导过程中粘膜tregs的扩张。此外，我们还发现在老年c-−缺陷小鼠体内存在Helios Foxp3+Tregs的优先积聚。这一意想不到的发现，以及在没有c-Rel和存在IL-2的情况下，幼稚的CD4+T细胞在体外转化为Tregs的观察，提供了一个证据，证明胸腺外诱导和外周Tregs(iTregs和pTregs)的产生独立于c-Rel。此外，用IL-2/抗IL-2单抗(JES6-1)处理后，野生型(WT)和Rel−/−小鼠的Helios+Foxp3+Treg细胞普遍增加。这些数据表明，外源性IL-2给药可以补偿c-Rel缺陷小鼠的IL-2产生缺陷和tTreg数量的减少。我们的发现表明，c-rel对tTregs的产生是必不可少的，但对pTregs和iTregs的产生并不是必需的。
The transcription factor c-Rel has been shown to be crucial for development of regulatory T cells (Tregs). Recent studies have reported that the expression of transcription factor Helios in Foxp3+ Tregs correlates with thymic origin of these cells (tTregs). Notably, we found that only the Helios+Foxp3+ Treg cell population was substantially reduced in c-Rel deficient mice. In contrast to a defective tTreg development, we observed an expansion of mucosal Tregs during the induction of acute colitis in rel−/− mice. Furthermore, we found a preferential accumulation of Helios−Foxp3+ Tregs in aged c-Rel deficient mice. This unexpected finding, together with the observation that naïve CD4+ T cells convert into Tregs in vitro in the absence of c-Rel and presence of IL-2, provide an evidence that extra-thymic generation of induced and peripheral Tregs (iTregs and pTregs) is independent of c-Rel. Moreover, the treatment with IL-2/anti-IL-2 mAb (JES6-1) resulted in a widespread increase of Helios+Foxp3+ Tregs in both wild-type (WT) and rel−/− mice. These data suggest that exogenous IL-2 administration compensates for defective IL-2 production and reduced tTreg numbers in c-Rel deficient mice. Our findings reveal that c-Rel is essential for the generation of tTregs but not for that of pTregs and iTregs.
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影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Honda K
影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf
影响因子：
10.5
作者：
KONTGEN, F;GRUMONT, RJ;GERONDAKIS, S
通讯作者：
GERONDAKIS, S
DOI：
10.1056/nejmoa1108188
发表时间：
2011-12-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Koreth J;Matsuoka K;Kim HT;McDonough SM;Bindra B;Alyea EP 3rd;Armand P;Cutler C;Ho VT;Treister NS;Bienfang DC;Prasad S;Tzachanis D;Joyce RM;Avigan DE;Antin JH;Ritz J;Soiffer RJ
通讯作者：
Soiffer RJ