Dual specificity phosphatase16 is a negative regulator of c-Jun NH2-terminal kinase activity in T cells

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 involvementinTcells has not yetbeendefined. Inthe 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). JNKactivity 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-γ 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-γ production. These results suggest that DUSP16 is an important regulator of JNK activity and effector functions of CD4 and CD8 T cells.