Abstract
MAPKs are evolutionarily conserved immune regulators. MAPK phosphatases (MKPs) that negatively regulate MAPK activities have recently emerged as critical players in both innate and adaptive immune responses. MKP-1, also known as DUSP1, was previously shown to negatively regulate innate immunity by inhibiting pro-inflammatory cytokine production. Here, we found that MKP-1 is necessary in T cell activation and function. MKP-1 deficiency in T cells impaired the activation, proliferation, and function of T cells in vitro, associated with enhanced activation of JNK and reduced NFATc1 translocation into the nucleus. Consistently, MKP-1-/- mice were defective in anti-influenza immunity in vivo and resistant to experimental autoimmune encephalomyelitis. Our results thus demonstrate that MKP-1 is a critical positive regulator of T cell activation and function and may be targeted in treatment of autoimmune diseases.
Original language | English (US) |
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Pages (from-to) | 30815-30824 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 284 |
Issue number | 45 |
DOIs | |
State | Published - Nov 6 2009 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
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