The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck
The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck
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DOI：
10.1038/ncomms4618
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发表时间：
2014-04-01
影响因子：
16.6
通讯作者：
Tan, Tse-Hua
中科院分区：
文献类型：
--
作者：
Li, Ju-Pi;Yang, Chia-Yu;Tan, Tse-Hua
JNK通路相关磷酸酶（JKAP，也称为DUSP 22或JSP-1）是一种JNK激活剂。JKAP在免疫调节中的体内作用尚不清楚。在这里，我们报告说，JKAP直接失活LCK的脱磷酸化酪氨酸-394残基在T细胞受体（TCR）信号。JKAP敲除的T细胞显示增强的细胞增殖和细胞因子产生。JKAP基因敲除小鼠表现出增强的T细胞介导的免疫应答，并且更容易患实验性自身免疫性脑脊髓炎（EAE）。此外，用JKAP敲除T细胞过继转移的受体小鼠显示出加重的EAE症状。老年JKAP基因敲除小鼠自发发生炎症和自身免疫。因此，我们的研究结果表明，JKAP是一种重要的磷酸酶，在TCR信号转导关闭阶段使Lck失活，导致T细胞介导的免疫和自身免疫的抑制。
JNK pathway-associated phosphatase (JKAP, also known as DUSP22 or JSP-1) is a JNK activator. The in vivo role of JKAP in immune regulation remains unclear. Here we report that JKAP directly inactivates Lck by dephosphorylating tyrosine-394 residue during T-cell receptor (TCR) signalling. JKAP-knockout T cells display enhanced cell proliferation and cytokine production. JKAP-knockout mice show enhanced T-cell-mediated immune responses and are more susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, the recipient mice that are adoptively transferred with JKAP-knockout T cells show exacerbated EAE symptoms. Aged JKAP-knockout mice spontaneously develop inflammation and autoimmunity. Thus, our results indicate that JKAP is an important phosphatase that inactivates Lck in the TCR signalling turn-off stage, leading to suppression of T-cell-mediated immunity and autoimmunity.