Title

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

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

8-18-2000

Document Type

Article

Medical Subject Headings

Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Cytokines; Hypersensitivity, Delayed; Immunity, Cellular; Leishmania major; Leishmaniasis, Cutaneous; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinases; T-Lymphocyte Subsets; Th1 Cells; Th2 Cells

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays important regulatory roles in helper T cell differentiation. In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice, despite their usually genetically resistant background, were unable to resolve 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 function. These findings demonstrate that the negative regulation of Th2 cytokine production by the JNK1 signaling pathway is essential for generating Th1-polarized immunity against intracellular pathogens, such as Leishmania major.

Rights and Permissions

Citation: J Immunol. 2000 Sep 1;165(5):2671-6.

Related Resources

Link to article in PubMed