MKP-1 is necessary for T cell activation and function.
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.
Zhang
Yongliang
Y
Department of Immunology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Reynolds
Joseph M
JM
Chang
Seon Hee
SH
Martin-Orozco
Natalia
N
Chung
Yeonseok
Y
Nurieva
Roza I
RI
Dong
Chen
C
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*
D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse