Mnk1 and 2 are dispensable for T cell development and activation but important for the pathogenesis of experimental autoimmune encephalomyelitis.
Mnk1 and 2 are dispensable for T cell development and activation but important for the pathogenesis of experimental autoimmune encephalomyelitis.
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MNK1和2对于T细胞的发育和激活是可分配的，但对于实验性自身免疫性脑脊髓炎的发病机理很重要。
DOI：
10.4049/jimmunol.1200026
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发表时间：
2013-02-01
期刊：
影响因子：
--
通讯作者：
Zhong XP
中科院分区：
文献类型：
--
作者：
Gorentla BK;Krishna S;Shin J;Inoue M;Shinohara ML;Grayson JM;Fukunaga R;Zhong XP
T细胞的发育和活化通常伴随着大量需要主动翻译的蛋白质的扩增和产生。真核生物翻译起始因子4 E（eIF 4 E）与mRNA的5'帽结构结合，并且对于帽依赖性翻译起始至关重要。已经假设MAPK相互作用激酶1和2（Mnk 1/2）通过在丝氨酸209（S209）处磷酸化eIF 4 E来促进帽依赖性翻译。利用抑制剂的药理学研究表明，Mnk 1/2在T细胞中发挥重要作用。然而，缺乏支持这一结论的遗传学证据。此外，调节T细胞中Mnk 1/2的信号通路仍不清楚。我们在这里证明了T细胞受体（TCR）接合激活原代T细胞中的Mnk 1/2。这种激活依赖于Ras-Erk 1/2信号传导，并被二酰甘油激酶α和β抑制。小鼠中Mnk 1/2双重缺陷消除了TCR诱导的eIF 4 E S209磷酸化，表明它们绝对需要eIF 4 E S209磷酸化。然而，Mnk 1/2双重缺陷不影响常规αβ T细胞、调节性T细胞或NKT细胞的发育。此外，T细胞活化，在体内的主要和记忆CD 8 T细胞对微生物感染的反应，和NKT细胞的细胞因子的产生没有明显改变Mnk 1/2缺陷。尽管Mnk 1/2缺陷导致在用完全弗洛伊德佐剂中的髓鞘少突胶质细胞糖蛋白肽免疫小鼠后CD 4 T细胞产生的IL-17和IFNγ减少，与较温和的实验性自身免疫性脑炎评分相关，但其不影响体外T辅助细胞分化。总之，这些数据表明，Mnk 1/2在T细胞发育和活化中发挥最小的作用，但可以调节非T细胞谱系以控制体内Th 1/Th 17分化。
T-cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5' cap structure of mRNA and is critical for cap-dependent translational initiation. It has been hypothesized that MAPK-interacting kinase 1 and 2 (Mnk1/2) promote cap-dependent translation by phosphorylating eIF4E at serine 209 (S209). Pharmacological studies utilizing inhibitors have suggested that Mnk1/2 play important roles in T-cells. However, genetic evidence supporting such conclusions is lacking. Moreover, the signaling pathways that regulate Mnk1/2 in T-cells remain unclear. We demonstrated here that T-cell receptor (TCR) engagement activates Mnk1/2 in primary T-cells. Such activation is dependent on Ras-Erk1/2 signaling and is inhibited by diacylglycerol kinases α and ζ. Mnk1/2 double deficiency in mice abolishes TCR-induced eIF4E S209 phosphorylation, indicating their absolute requirement for eIF4E S209 phosphorylation. However, Mnk1/2 double deficiency does not affect the development of conventional αβ T-cells, regulatory T-cells, or NKT-cells. Furthermore, T-cell activation, in vivo primary and memory CD8 T-cell responses to microbial infection, and NKT-cell cytokine production were not obviously altered by Mnk1/2 deficiency. Although Mnk1/2 deficiency causes decreased IL-17 and IFNγ production by CD4 T-cells following immunization of mice with myelin oligodendrocyte glycoprotein peptide in complete Freud's adjuvant, correlating with milder experimental autoimmune encephalitis scores, it does not affect T helper cell differentiation in vitro. Together, these data suggest that Mnk1/2 play a minimal role in T-cell development and activation but may regulate non-T-cell lineages to control Th1/Th17 differentiation in vivo.
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影响因子：
14.9
作者：
Chen YJ;Tan BC;Cheng YY;Chen JS;Lee SC
通讯作者：
Lee SC
DOI：
10.1073/pnas.1005320107
发表时间：
2010-08-10
影响因子：
11.1
作者：
Furic, Luc;Rong, Liwei;Sonenberg, Nahum
通讯作者：
Sonenberg, Nahum
DOI：
10.2741/3136
发表时间：
2008-05-01
期刊：
FRONTIERS IN BIOSCIENCE
影响因子：
--
作者：
Gaestel, Matthias
通讯作者：
Gaestel, Matthias
影响因子：
20.3
作者：
Gorentla, Balachandra K.;Wan, Chi-Keung;Zhong, Xiao-Ping
通讯作者：
Zhong, Xiao-Ping
影响因子：
11.4
作者：
Fukunaga, R;Hunter, T
通讯作者：
Hunter, T