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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


  • Zhao H
  • Yan M
  • Wang H
  • Erickson S
  • Grewal IS
  • Dixit VM


The Journal of experimental medicine

Publication Data

November 19, 2001

Associated Grants


Mesh Terms

  • 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