Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals.
Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals.
复制标题
DOI：
10.1016/j.immuni.2013.02.022
复制
发表时间：
2013-06-27
期刊：
影响因子：
32.4
通讯作者：
Singer A
中科院分区：
文献类型：
--
作者：
Tai X;Erman B;Alag A;Mu J;Kimura M;Katz G;Guinter T;McCaughtry T;Etzensperger R;Feigenbaum L;Singer DS;Singer A
免疫耐受需要调节性T（Treg）细胞来预防自身免疫性疾病，转录因子Foxp 3作为Treg细胞发育和功能的关键调节因子发挥作用。我们在此报道Foxp 3对胸腺中发育中的Treg细胞是致命的，因为它诱导了独特的促凋亡蛋白特征（Puma++p-Bim++p-JNK++ DUSP 6-）并抑制促存活Bcl-2分子的表达。然而，Foxp 3致死性被常见的γ链（γc）依赖性细胞因子信号阻止，这些信号以仅足以支持约100万个Treg细胞的有限量存在于胸腺中。因此，胸腺中大多数新产生的Treg细胞被剥夺了这种信号，并经历了Foxp 3诱导的死亡，其中Foxp 3 + CD 25- Treg前体细胞是最敏感的。因此，我们确定Foxp 3是一种促凋亡蛋白，需要发育中的Treg细胞相互竞争，以限制胸腺中γ c依赖性存活信号的量。
Immune tolerance requires regulatory T (Treg) cells to prevent autoimmune disease, with the transcription factor Foxp3 functioning as the critical regulator of Treg cell development and function. We report here that Foxp3 was lethal to developing Treg cells in the thymus because it induced a unique pro-apoptotic protein signature (Puma++p-Bim++p-JNK++DUSP6-) and repressed expression of pro-survival Bcl-2 molecules. However, Foxp3 lethality was prevented by common gamma chain (γc)-dependent cytokine signals that were present in the thymus in limiting amounts sufficient to support only ~1 million Treg cells. Consequently, most newly arising Treg cells in the thymus were deprived of this signal and underwent Foxp3-induced death, with Foxp3+CD25- Treg precursor cells being the most susceptible. Thus, we identify Foxp3 as a pro-apoptotic protein that requires developing Treg cells to compete with one another for limiting amounts of γc-dependent survival signals in the thymus.
登录
查看更多内容
影响因子：
64.8
作者：
Marson, Alexander;Kretschmer, Karsten;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
影响因子：
7.8
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
通讯作者：
Ham, Jonathan
影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
DOI：
10.4049/jimmunol.181.1.225
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bayer AL;Lee JY;de la Barrera A;Surh CD;Malek TR
通讯作者：
Malek TR