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Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5
Zhang Y.1; Blattman J.N.1; Kennedy N.J.4; Duong J.1; Hguyen T.1; Wang Y.1; Davis R.J.4; Greenberg P.D.1; Flavell R.A.2; Dong C.1
2004-08-12
Source PublicationNature
ISSN00280836
Volume430Issue:7001Pages:793-797
AbstractMitogen-activated protein (MAP) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. MAP kinase phosphatase (MKP) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. A number of mammalian MKPs have been identified so far, but their specific physiological functions in negative regulation of MAP kinases have not been genetically defined. Here we examine innate and adaptive immune responses in the absence of MKP5. JNK activity was selectively increased in Mkp5 (also known as Dusp10)-deficient mouse cells. Mkp5-deficient cells produced greatly enhanced levels of pro-inflammatory cytokines during innate immune responses and exhibited greater T-cell activation than their wild-type counterparts. However, Mkp5-deficient T cells proliferated poorly upon activation, which resulted in increased resistance to experimental autoimmune encephalomyelitis. By contrast, Mkp5-deficient CD4 and CD8 effector T cells produced significantly increased levels of cytokines compared with wild-type cells, which led to much more robust and rapidly fatal immune responses to secondary infection with lymphocytic choriomeningitis virus. Therefore, MKP5 has a principal function in both innate and adaptive immune responses, and represents a novel target for therapeutic intervention of immune diseases.
DOI10.1038/nature02764
URLView the original
Language英語
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Cited Times [WOS]:171   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.University of Washington, Seattle
2.Yale University
3.University of Texas MD Anderson Cancer Center
4.University of Massachusetts Medical School
Recommended Citation
GB/T 7714
Zhang Y.,Blattman J.N.,Kennedy N.J.,et al. Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5[J]. Nature,2004,430(7001):793-797.
APA Zhang Y..,Blattman J.N..,Kennedy N.J..,Duong J..,Hguyen T..,...&Dong C..(2004).Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5.Nature,430(7001),793-797.
MLA Zhang Y.,et al."Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5".Nature 430.7001(2004):793-797.
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