Transcriptional coregulator Ess2 controls survival of post-thymic CD4(+) T cells through the Myc and IL-7 signaling pathways.
Transcriptional coregulator Ess2 controls survival of post-thymic CD4(+) T cells through the Myc and IL-7 signaling pathways.
复制标题
DOI：
10.1016/j.jbc.2022.102342
复制
发表时间：
2022-09
影响因子：
4.8
通讯作者：
Makishima, Makoto
中科院分区：
文献类型：
--
作者：
Takada, Ichiro;Hidano, Shinya;Takahashi, Sayuri;Yanaka, Kaori;Ogawa, Hidesato;Tsuchiya, Megumi;Yokoyama, Atsushi;Sato, Shingo;Ochi, Hiroki;Nakagawa, Tohru;Kobayashi, Takashi;Nakagawa, Shinichi;Makishima, Makoto
CD 12，也称为Dgcr 14，是CD 4 + T细胞的转录共调节因子。22q11.2缺失综合征（22 q11 DS）与22q11.2缺失相关，22 q11 DS可导致心脏缺陷、骨骼异常和免疫缺陷。然而，22 q11 DS与p53 2的具体关联仍不清楚。为了阐明CD 42在T细胞发育中的作用，我们使用Cre/loxP系统产生了CD 42 floxed（CD 42 fl/fl）和CD 4 + T细胞特异性CD 42 KO（CD 42 Δ CD 4/Δ CD 4）小鼠。有趣的是，Δ 2 Δ CD 4/Δ CD 4小鼠脾脏中的幼稚T细胞数量减少，而胸腺中的胸腺细胞（CD 4 − CD 8 −、CD 4 + CD 8+、CD 4 + CD 8 −和CD 4 − CD 8+）数量保持不变。此外，Δ 2 Δ CD 4/Δ CD 4小鼠胸腺和脾脏中的NKT细胞减少，γδT细胞增加。使用RNA-seq进行的全基因组表达分析显示，CD 42缺失改变了CD 4单阳性胸腺细胞中许多基因的表达，包括与免疫系统相关的基因和Myc靶基因。此外，c-Myc基因的转录活性也受到抑制。在小鼠中被鉴定为ESS 2靶标的一些基因显示出与人类免疫细胞中的ESS 2的表达相关性。此外，Δ 2 Δ CD 4/Δ CD 4初始CD 4 + T细胞在响应IL-7时不能维持存活。我们的研究结果表明，CD 402通过Myc和IL-7信号通路在胸腺后T细胞存活中起着关键作用。
Ess2, also known as Dgcr14, is a transcriptional co-regulator of CD4+ T cells. Ess2 is located in a chromosomal region, the loss of which has been associated with 22q11.2 deletion syndrome (22q11DS), which causes heart defects, skeletal abnormalities, and immunodeficiency. However, the specific association of Ess2 with 22q11DS remains unclear. To elucidate the role of Ess2 in T-cell development, we generated Ess2 floxed (Ess2fl/fl) and CD4+ T cell–specific Ess2 KO (Ess2ΔCD4/ΔCD4) mice using the Cre/loxP system. Interestingly, Ess2ΔCD4/ΔCD4 mice exhibited reduced naïve T-cell numbers in the spleen, while the number of thymocytes (CD4−CD8−, CD4+CD8+, CD4+CD8−, and CD4−CD8+) in the thymus remained unchanged. Furthermore, Ess2ΔCD4/ΔCD4 mice had decreased NKT cells and increased γδT cells in the thymus and spleen. A genome-wide expression analysis using RNA-seq revealed that Ess2 deletion alters the expression of many genes in CD4 single-positive thymocytes, including genes related to the immune system and Myc target genes. In addition, Ess2 enhanced the transcriptional activity of c-Myc. Some genes identified as Ess2 targets in mice show expressional correlation with ESS2 in human immune cells. Moreover, Ess2ΔCD4/ΔCD4 naïve CD4+ T cells did not maintain survival in response to IL-7. Our results suggest that Ess2 plays a critical role in post-thymic T-cell survival through the Myc and IL-7 signaling pathways.
登录
查看更多内容
DOI：
10.1621/nrs.07003
发表时间：
2009
期刊：
Nuclear receptor signaling
影响因子：
--
作者：
Jetten AM
通讯作者：
Jetten AM
影响因子：
1.6
作者：
McDonald-McGinn, Donna M.;Sullivan, Kathleen E.
通讯作者：
Sullivan, Kathleen E.
影响因子：
16
作者：
Hegele, Anna;Kamburov, Atanas;Stelzl, Ulrich
通讯作者：
Stelzl, Ulrich
影响因子：
4.9
作者：
Carey, Rebecca;Jurickova, Ingrid;Denson, Lee A.
通讯作者：
Denson, Lee A.
影响因子：
16
作者：
Kalkat, Manpreet;Resetca, Diana;Penn, Linda Z.
通讯作者：
Penn, Linda Z.