The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of autoimmune T cells.
The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of autoimmune T cells.
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DOI：
10.1016/j.immuni.2014.09.017
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发表时间：
2014-10-16
期刊：
影响因子：
32.4
通讯作者：
Siebenlist, Ulrich
中科院分区：
文献类型：
--
作者：
Tang, Wanhu;Wang, Hongshan;Claudio, Estefania;Tassi, Ilaria;Ha, Hye-lin;Saret, Sun;Siebenlist, Ulrich
Bcl-3是i -κ b家族的非典型成员，通过与p50 （NF-κB1）或p52 （NF-κB2）同源二聚体的关联来调节细胞核中的转录。尽管有证据证明Bcl-3的整体生理重要性，但对其细胞特异性功能或机制知之甚少。在这里，我们证明了Bcl-3在自身免疫中的T细胞内在功能。bcl -3缺陷T细胞在T细胞转移性结肠炎和实验性自身免疫性脑脊髓炎中不能诱导疾病。对疾病的保护与产生细胞因子IFNγ-和GM-CSF的Th1细胞的减少和Th17细胞的增加相关。虽然在缺乏Bcl-3的情况下，分化为Th1细胞的过程没有受到阻碍，但分化后的Th1细胞会转化为致病性较低的th17样细胞，这在一定程度上是通过rorγ - t转录因子的表达机制实现的。因此，Bcl-3通过阻断向th17样细胞的转化来限制Th1细胞的可塑性并促进致病性，揭示了一种形成适应性免疫的独特调节类型。
Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFNγ- and GM-CSF, and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less pathogenic Th17-like cells, in part via mechanisms involving expression of the RORγt transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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影响因子：
7.3
作者：
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通讯作者：
Levings MK
DOI：
10.1084/jem.187.2.147
发表时间：
1998-01-19
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Franzoso G;Carlson L;Poljak L;Shores EW;Epstein S;Leonardi A;Grinberg A;Tran T;Scharton-Kersten T;Anver M;Love P;Brown K;Siebenlist U
通讯作者：
Siebenlist U
影响因子：
37.3
作者：
Maldonado V;Melendez-Zajgla J
通讯作者：
Melendez-Zajgla J