Impaired c-Jun amino terminal kinase activity and T cell differentiation in death receptor 6-deficient mice.
During an immune response naive T helper (Th) cells differentiate into two functionally distinct subsets, Th1 and Th2, based on their cytokine secretion profile and immunomodulatory function. c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. We have recently identified a TNFR superfamily death domain-containing molecule, death receptor (DR)6, which potently activates JNK. T cells from DR6-deficient mice are substantially impaired in JNK activation. When DR6(-/-) mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. In addition, DR6(-/)- T cells showed preference toward Th2 differentiation in vitro. The phenotype seen in the DR6(-/)- mice is not due to the apoptotic pathway. Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response. This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general.
Pubmed ID: 11714751 RIS Download
Amino Acid Sequence | Animals | Apoptosis | Cell Differentiation | Cloning, Molecular | Female | Immunoglobulin E | Immunoglobulin G | JNK Mitogen-Activated Protein Kinases | Male | Mice | Mice, Inbred C57BL | Mitogen-Activated Protein Kinases | Molecular Sequence Data | Receptors, Tumor Necrosis Factor | T-Lymphocytes