Defective T cell differentiation in the absence of Jnk1

The c-Jun NH₂-terminal kinase (JNK) signaling pathway has been implicated in the immune response that is mediated by the activation and differentiation of CD4 helper T (T(H)) cells into T(H)1 and T(H)2 effector cells. JNK activity observed in wild-type activated T(H) cells was severely reduced in T(H) cells from Jnk1^-1- mice. The Jnk1^-1- T cells hyperproliferated, exhibited decreased activation-induced cell death, and preferentially differentiated to T(H)2 cells. The enhanced production of T(H)2 cytokines by Jnk1^-1- cells was associated with increased nuclear accumulation of the transcription factor NFATc. Thus, the JNK1 signaling pathway plays a key role in T cell receptor-initiated T(H) cell proliferation, apoptosis, and differentiation.