TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway
TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway
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跨高尔基体网络的 TRAF3IP3 通过 MEK/ERK 信号通路调节 NKT2 成熟
DOI：
10.1038/s41423-019-0234-0
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发表时间：
2019-05
影响因子：
24.1
通讯作者：
Ge Qing
中科院分区：
文献类型：
--
作者：
Zhang Xinwei;Wang Ke;Zhao Weijia;Cao Li;Zhang Shusong;Jin Rong;Sun Xiuyuan;Hao Jie;Huang Xiaojun;Zhu Mingzhao;Wu Hounan;Zhao Hongshan;Ge Qing
胸腺自然杀伤T（NKT）2细胞是一类具有PLZF~（hi）GATA ~（3 ~（hi）IL-4~+）的非变异性NKT细胞，其分化机制尚不完全清楚。我们报告了TRAF 3相互作用蛋白3的重要作用，（TRAF 3 IP 3）在胸腺髓质中定向NKT 2的功能成熟和扩增中的作用。TRAF 3 IP 3特异性缺失导致胸腺NKT 2细胞减少，产生IL-4的外周iNKT减少，CD 24 + CD 44 ~-和CCR 7 ~+ CD 44 ~-未成熟iNKT的阳性选择和PLZF高表达不受影响，只有CD 44 ~（hi）NK1.1~-Traf 3 ip 3 ~（-/-）小鼠的iNKT在刺激后表现出Egr 2、PLZF和IL-17 RB的表达减少，增殖减少，IL-4的产生减少。和TRAF 3 IP 3在trans-Golgi网络中募集MEK 1并促进ERK磷酸化和核转位。这些数据表明，在NKT 2分化过程中，一个重要的功能成熟过程是由trans-Golgi网络中的MEK/ERK信号调节的。
Thymic natural killer T(NKT)2 cells are a subset of invariant NKT cells with PLZF~(hi)GATA3~(hi)IL-4~+.The differentiation of NKT2 cells is not fully understood.In the present study, we report an important role of TRAF3-interacting protein 3(TRAF3IP3)in the functional maturation and expansion of committed NKT2s in thymic medulla.Mice with T-cell-specific deletion of TRAF3IP3 had decreased thymic NKT2 cells, decreased IL-4-producing peripheral iNKTs, and defects in response to α-galactosylceramide.Positive selection and high PLZF expression in CD24+CD44~-and CCR7~+CD44~-immature iNKTs were not affected.Only CD44~(hi)NK1.1~-iNKTs in Traf3ip3~(-/-)mice showed reduced expression of Egr2, PLZF, and IL-17RB, decreased proliferation, and reduced IL-4 production upon stimulation.This Egr2 and IL-4 expression was augmented by MEK1/ERK activation in iNKTs, and TRAF3IP3 at the trans-Golgi network recruited MEK1 and facilitated ERK phosphorylation and nuclear translocation.LTβR-regulated bone marrow-derived nonlymphoid cells in the medullary thymic microenvironment were required for MEK/ERK activation and NKT2 maturation.These data demonstrate an important functional maturation process in NKT2 differentiation that is regulated by MEK/ERK signaling at the trans-Golgi network.
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DOI：
10.1084/jem.20022234
发表时间：
2003-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sivakumar V;Hammond KJ;Howells N;Pfeffer K;Weih F
通讯作者：
Weih F
DOI：
10.4049/jimmunol.1501609
发表时间：
2016-04
期刊：
The Journal of Immunology
影响因子：
--
作者：
Dimitra Vyrla;G. Nikolaidis;F. Oakley;M. Perugorria;P. Tsichlis;D. Mann;A. Eliopoulos
通讯作者：
Dimitra Vyrla;G. Nikolaidis;F. Oakley;M. Perugorria;P. Tsichlis;D. Mann;A. Eliopoulos
影响因子：
16.6
作者：
Georgiev, Hristo;Ravens, Inga;Benarafa, Charaf;Foerster, Reinhold;Bernhardt, Guenter
通讯作者：
Bernhardt, Guenter
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
16.6
作者：
Kimura MY;Igi A;Hayashizaki K;Mita Y;Shinzawa M;Kadakia T;Endo Y;Ogawa S;Yagi R;Motohashi S;Singer A;Nakayama T
通讯作者：
Nakayama T