title: MKP-1 is necessary for T cell activation and function.
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.
authors.affiliation: Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Reynolds
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Orozco
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
authors.forename: Roza I
authors.initials: RI
authors.lastname: Nurieva
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009980:Influenza A virus / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D021381:Protein Transport; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
chemical_list: D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse