MAP kinase phosphatase 1 is necessary for T cell activation and function (35.1)

Abstract

Abstract Mitogen-activated protein kinases (MAPK) are evolutionary conserved immune regulators. MAPK phosphatases that negatively regulate MAPK activities have emerged as important 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 positively regulate T cell activation, function and negatively regulate apoptosis. MKP1-deficient dendritic cells exhibited significantly reduced ability to activate T cells than wild-type cells. In T cells, MKP-1 deficiency led to enhanced activation of ERK and JNK but not p38, and impaired the activation, proliferation and function of T cells in vitro and in vivo. MKP-1 deficient T cells exhibited enhanced activation induced cell death. Consistently, MKP-1-/- mice were found to be resistant to experimental autoimmune encephalomyelitis but were defective in anti-influenza immunity in vivo. Our results thus demonstrate MKP-1 as a critical positive regulator of T cell activation and function and may be targeted in treatment of immune diseases.