The JNK pathway regulates the In vivo deletion of immature CD4(+)CD8(+) thymocytes.
The JNK pathway regulates the In vivo deletion of immature CD4(+)CD8(+) thymocytes.
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DOI：
10.1084/jem.188.10.1817
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发表时间：
1998-11-16
期刊：
影响因子：
--
通讯作者：
Flavell RA
中科院分区：
文献类型：
--
作者：
Rincón M;Whitmarsh A;Yang DD;Weiss L;Dérijard B;Jayaraj P;Davis RJ;Flavell RA
细胞外信号调节激酶（ERK）、c-Jun NH 2-末端激酶（JNK）和p38 MAP激酶途径在抗原特异性T细胞受体（TCR）的连接后被触发。在胸腺中T细胞的发育过程中，ERK通路是CD 4 − CD 8 −分化为CD 4 + CD 8+双阳性（DP）胸腺细胞、DP细胞的阳性选择及其成熟为CD 4+细胞所必需的。然而，ERK通路不是负选择所必需的。在这里，我们表明，JNK激活DP胸腺细胞在体内的信号，启动负选择。这些细胞中JNK的激活似乎是由MAP激酶激酶MKK 7介导的，因为在胸腺细胞中检测到高水平的MKK 7和低水平的Sek-1/MKK 4基因表达。使用显性阴性JNK转基因小鼠，我们表明，抑制JNK途径减少体内缺失的DP胸腺细胞。此外，在这些小鼠中，DP胸腺细胞对细胞死亡的抵抗力增加，导致体内DP消除后正常胸腺细胞群的重建加速。总之，这些数据表明JNK途径通过响应于TCR衍生的和其他胸腺环境介导的信号的细胞凋亡而导致DP胸腺细胞的缺失。
The extracellular signal-regulated kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways are triggered upon ligation of the antigen-specific T cell receptor (TCR). During the development of T cells in the thymus, the ERK pathway is required for differentiation of CD4−CD8− into CD4+CD8+ double positive (DP) thymocytes, positive selection of DP cells, and their maturation into CD4+ cells. However, the ERK pathway is not required for negative selection. Here, we show that JNK is activated in DP thymocytes in vivo in response to signals that initiate negative selection. The activation of JNK in these cells appears to be mediated by the MAP kinase kinase MKK7 since high levels of MKK7 and low levels of Sek-1/MKK4 gene expression were detected in thymocytes. Using dominant negative JNK transgenic mice, we show that inhibition of the JNK pathway reduces the in vivo deletion of DP thymocytes. In addition, the increased resistance of DP thymocytes to cell death in these mice produces an accelerated reconstitution of normal thymic populations upon in vivo DP elimination. Together, these data indicate that the JNK pathway contributes to the deletion of DP thymocytes by apoptosis in response to TCR-derived and other thymic environment– mediated signals.
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DOI：
10.1084/jem.185.2.263
发表时间：
1997-01-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kishimoto H;Sprent J
通讯作者：
Sprent J
影响因子：
15.3
作者：
KISHIMOTO, H;SURH, CD;SPRENT, J
通讯作者：
SPRENT, J
影响因子：
64.5
作者：
Field, SJ;Tsai, FY;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
56.9
作者：
LEE, SL;WESSELSCHMIDT, RL;MILBRANDT, J
通讯作者：
MILBRANDT, J
影响因子：
4.8
作者：
Chen, YR;Meyer, CF;Tan, TH
通讯作者：
Tan, TH