Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Microbiol Immunol. 2010 Feb;54(2):105-11. doi: 10.1111/j.1348-0421.2009.00188.x.
Activation of MAPK is negatively regulated by DUSP, which dephosphorylate the phosphothreonine and phosphotyrosine residues. We have identified a novel JNK-specific DUSP, DUSP16, from murine macrophages. Its involvement in T cells has not yet been defined. In the present study, we found expression of DUSP16 in thymocytes and activated T cells but not in naive T cells. To elucidate the roles of DUSP16 in T cells, transgenic mice expressing a dominant negative form of DUSP16 specifically in T cells were generated (dnDUSP16 Tg). JNK activity was selectively augmented in the thymocytes of these dnDUSP16 Tg mice. CD4 T cells in dnDUSP16 Tg mice showed normal levels of proliferation and IL-2 production after TCR triggering, while they produced increased IFN-gamma but reduced Th2 cytokines compared with wild type CD4 T cells. On the other hand CD8 T cells in dnDUSP16 Tg mice produced an increased amount of IL-2, which resulted in enhanced proliferation and IFN-gamma production. These results suggest that DUSP16 is an important regulator of JNK activity and effector functions of CD4 and CD8 T cells.
MAPK 的激活受到 DUSP 的负调控，DUSP 可使磷酸苏氨酸和磷酸酪氨酸残基去磷酸化。我们从鼠巨噬细胞中鉴定出一种新型的 JNK 特异性 DUSP，即 DUSP16。其在 T 细胞中的作用尚未确定。在本研究中，我们发现 DUSP16 在胸腺细胞和活化的 T 细胞中表达，但在幼稚的 T 细胞中不表达。为了阐明 DUSP16 在 T 细胞中的作用，我们生成了在 T 细胞中特异性表达显性负形式 DUSP16 的转基因小鼠（dnDUSP16 Tg）。这些 dnDUSP16 Tg 小鼠的胸腺细胞中 JNK 活性被选择性增强。dnDUSP16 Tg 小鼠的 CD4 T 细胞在 TCR 触发后表现出正常的增殖和 IL-2 产生水平，但与野生型 CD4 T 细胞相比，它们产生增加的 IFN-γ但减少 Th2 细胞因子。另一方面，dnDUSP16 Tg 小鼠的 CD8 T 细胞产生更多的 IL-2，导致增殖和 IFN-γ产生增强。这些结果表明 DUSP16 是 JNK 活性和 CD4 和 CD8 T 细胞效应功能的重要调节剂。
