Journal
JOURNAL OF IMMUNOLOGY
Volume 192, Issue 4, Pages 1547-1557Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300989
Keywords
-
Categories
Funding
- National Health Research Institutes, Taiwan [98A1-IMPP01-014]
- Taichung Veterans General Hospital [TVGH-NHRI01]
Ask authors/readers for more resources
T cell activation is dependent upon phosphorylation of MAPKs, which play a critical role in the regulation of immune responses. Dual-specificity phosphatase 14 (DUSP14; also known as MKP6) is classified as a MAPK phosphatase. The in vivo functions of DUSP14 remain unclear. Thus, we generated DUSP14-deficient mice and characterized the roles of DUSP14 in T cell activation and immune responses. DUSP14 deficiency in T cells resulted in enhanced T cell proliferation and increased cytokine production upon T cell activation. DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser(438), leading to TAB1-TAK1 complex inactivation in T cells. The phosphorylation levels of the TAB1-TAK1 complex and its downstream molecules, including JNK and IkB kinase, were enhanced in DUSP14-deficient T cells upon stimulation. The enhanced JNK and I kappa B kinase activation in DUSP14-deficient T cells was attenuated by TAB1 short hairpin RNA knockdown. Consistent with that, DUSP14-deficient mice exhibited enhanced immune responses and were more susceptible to experimental autoimmune encephalomyelitis induction. Thus, DUSP14 negatively regulates TCR signaling and immune responses by inhibiting TAB1 activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available