JNK1 is required for T cell-mediated immunity against Leishmania major infection

c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that pl ays important regulatory roles in helper T cell differentiation. In the cur rent study, we used Jnk1-deficient mice to examine the function of JNK duri ng an in vivo pathogenic infection, leishmaniasis, which is strongly influe nced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice , despite their usually genetically resistant background, mere unable to re solve Leishmania infections, Jnk1(-/-) mice displayed reduced delayed-type hypersensitivity in response to the pathogen, which was associated with a T cell defect,We found that, although these mice can direct an apparent Th1- response, there is also simultaneous generation of Leishmania-specific Th2 responses, which possibly down-modulate protective Th1-mediated immune func tion. These findings demonstrate that the negative regulation of Th2 cytoki ne production by the JNK1 signaling pathway is essential for generating Th1 -polarized immunity against intracellular pathogens, such as Leishmania maj or.