JNK is required for effector T-cell function but not for T-cell activation.
The hallmark of T-cell activation is the production of interleukin 2 (IL-2). c-Jun amino-terminal kinase (JNK), a MAP kinase that phosphorylates c-Jun and other components of the AP-1 group of transcription factors, has been implicated in the activation of IL-2 expression. Previously, we found that T cells from mice deficient in the Jnk1 or Jnk2 gene can be activated and produce IL-2 normally, but are deficient in functional differentiation into Th1 or Th2 subsets. However, studies of mice with compound mutations indicate that JNK1 and JNK2 are redundant during mouse development. Here we use three new mouse models in which peripheral T cells completely lack JNK proteins or signalling, to test whether the JNK signalling pathway is crucial for IL-2 expression and T-cell activation. Unexpectedly, these T cells made more IL-2 and proliferated better than wild-type cells. However, production of effector T-cell cytokines did require JNK. Thus, JNK is necessary for T-cell differentiation but not for naive T-cell activation.
Dong
C
C
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Yang
D D
DD
Tournier
C
C
Whitmarsh
A J
AJ
Xu
J
J
Davis
R J
RJ
Flavell
R A
RA
D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D013234:Stem Cells; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D007376:Interleukin-2; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases