Back to Search
Start Over
Functional involvement of dual specificity phosphatase 16 (DUSP16), a c-Jun N-terminal kinase-specific phosphatase, in the regulation of T helper cell differentiation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2011 Jul 15; Vol. 286 (28), pp. 24896-905. Date of Electronic Publication: 2011 May 25. - Publication Year :
- 2011
-
Abstract
- Naïve CD4(+) T helper (Th) cells differentiate into distinct subsets of effector cells (Th1, Th2, Th17, and induced regulatory T cells (iTreg)) expressing different sets of cytokines upon encounter with presented foreign antigens. It has been well established that Th1/Th2 balance is critical for the nature of the following immune responses. Previous reports have demonstrated important roles of c-Jun N-terminal kinase (JNK) in Th1/Th2 balance, whereas the regulatory mechanisms of JNK activity in Th cells have not been elucidated. Here, we show that dual specificity phosphatase 16 (DUSP16, also referred to as MKP-M or MKP-7), which preferentially inactivates JNK, is selectively expressed in Th2 cells. In the in vitro differentiation assay of naïve CD4(+) cells, DUSP16 expression is up-regulated during Th2 differentiation and down-regulated during Th1 differentiation. Chromatin immunoprecipitation revealed the increased acetylation of histone H3/H4 at the dusp16 gene promoter in CD4(+) T cells under the Th2 condition. Adenoviral transduction of naïve CD4(+) T cells with DUSP16 resulted in increased mRNA expression of IL-4 and GATA-3 in Th2 and decreased expression of IFNγ and T-bet in Th1 differentiation. In contrast, transduction of a dominant negative form of DUSP16 had the reverse effects. Furthermore, upon immunization, T cell-specific dusp16 transgenic mice produced antigen-specific IgG2a at lower amounts, whereas DN dusp16 transgenic mice produced higher amounts of antigen-specific IgG2a accompanied by decreased amounts of antigen-specific IgG1 and IgE than those of control mice. Together, these data suggest the functional role of DUSP16 in Th1/Th2 balance.
- Subjects :
- Acetylation
Animals
Dual-Specificity Phosphatases genetics
Dual-Specificity Phosphatases immunology
Female
GATA3 Transcription Factor biosynthesis
GATA3 Transcription Factor genetics
GATA3 Transcription Factor immunology
Histones genetics
Histones immunology
Histones metabolism
Immunoglobulin G genetics
Immunoglobulin G immunology
Immunoglobulin G metabolism
Interferon-gamma biosynthesis
Interferon-gamma genetics
Interferon-gamma immunology
Interleukin-4 biosynthesis
Interleukin-4 genetics
Interleukin-4 immunology
JNK Mitogen-Activated Protein Kinases genetics
JNK Mitogen-Activated Protein Kinases immunology
JNK Mitogen-Activated Protein Kinases metabolism
Mice
Mice, Inbred BALB C
Mice, Transgenic
Mitogen-Activated Protein Kinase Phosphatases genetics
Mitogen-Activated Protein Kinase Phosphatases immunology
T-Box Domain Proteins genetics
T-Box Domain Proteins immunology
T-Box Domain Proteins metabolism
Th1 Cells cytology
Th1 Cells immunology
Th2 Cells cytology
Th2 Cells immunology
Cell Differentiation physiology
Dual-Specificity Phosphatases metabolism
Gene Expression Regulation, Enzymologic physiology
Mitogen-Activated Protein Kinase Phosphatases metabolism
Th1 Cells enzymology
Th2 Cells enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 286
- Issue :
- 28
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21613215
- Full Text :
- https://doi.org/10.1074/jbc.M111.245019