Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis.
Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis.
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T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
DOI：
10.1084/jem.20031819
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发表时间：
2004-07-05
影响因子：
15.3
通讯作者：
Kuchroo, VK
中科院分区：
文献类型：
--
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
转录因子信号转导子和转录激活子（STAT）1以及T - bet控制产生干扰素（IFN）-γ的辅助性T细胞1型（Th1）细胞的分化。在此我们比较T - bet和STAT1在实验性自身免疫性脑脊髓炎（EAE）的起始和调控中的作用，EAE是一种由Th1细胞引发的疾病。用髓鞘少突胶质细胞糖蛋白（MOG）免疫的T - bet缺陷型小鼠对EAE的发生具有抵抗力。当T - bet - / - 小鼠与MOG特异性2D2 T细胞受体转基因品系杂交时，也观察到这种保护作用。相反，尽管T - bet位于STAT1的下游，但STAT1 - / - 小鼠对EAE高度易感，并发展出更严重且加速的疾病，伴有非典型神经病理特征。T - bet的功能占主导地位，因为T - bet和STAT1两者均缺陷的小鼠也能免受EAE的侵害。来自这两种小鼠品系的CD4 + CD25 + 调节性T细胞功能完全正常，不能解释疾病易感性的差异。然而，STAT1 - / - 小鼠中EAE的加重与持续产生分泌IFN - γ的Th1细胞以及负责中枢神经系统中巨噬细胞和中性粒细胞募集增加的选择性趋化因子的上调有关。尽管STAT1和T - bet这两种转录因子都诱导IFN - γ基因转录，但我们的结果表明它们在调节致病性Th1细胞应答中的功能存在显著差异。
The transcription factors signal transducer and activator of transcription (STAT)1 and T-bet control the differentiation of interferon (IFN)-γ–producing T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a disease initiated by Th1 cells. T-bet–deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This protection was also observed when T-bet−/− mice were crossed to the MOG-specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is downstream of STAT1, STAT1−/− mice were highly susceptible to EAE and developed more severe and accelerated disease with atypical neuropathologic features. The function of T-bet was dominant as mice deficient in both T-bet and STAT1 were also protected from EAE. CD4+ CD25+ regulatory T cells from these two mice strains were fully competent and do not explain the difference in disease susceptibility. However, enhanced EAE in STAT1−/− mice was associated with continued generation of IFN-γ–producing Th1 cells and up-regulation of selective chemokines responsible for the increased recruitment of macrophages and neutrophils in the central nervous system. Although the two transcription factors, STAT1 and T-bet, both induce IFN-γ gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses.
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影响因子：
4.4
作者：
Tran, EH;Prince, EN;Owens, T
通讯作者：
Owens, T
影响因子：
56.9
作者：
Szabo, SJ;Sullivan, BM;Glimcher, LH
通讯作者：
Glimcher, LH
DOI：
10.1097/00001665-199307000-00013
发表时间：
1993-07-01
期刊：
The Journal of craniofacial surgery
影响因子：
--
作者：
Barone, C M;Ferder, M;Argamaso, R V
通讯作者：
Argamaso, R V
影响因子：
3.1
作者：
Diab, A;Abdalla, H;Link, H
通讯作者：
Link, H
影响因子：
30.5
作者：
Afkarian, M;Sedy, JR;Murphy, KM
通讯作者：
Murphy, KM