Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5

Yongliang Zhang, Joseph Blattman, Norman J. Kennedy, Julie Duong, Thang Hguyen, Ying Wang, Roger J. Davis, Philip D. Greenberg, Richard A. Flavell, Chen Dong

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Mitogen-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.

Original languageEnglish (US)
Pages (from-to)793-797
Number of pages5
JournalNature
Volume430
Issue number7001
DOIs
StatePublished - Aug 12 2004
Externally publishedYes

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Mitogen-Activated Protein Kinase Phosphatases
Adaptive Immunity
Innate Immunity
Mitogen-Activated Protein Kinases
T-Lymphocytes
Dual-Specificity Phosphatases
Cytokines
Lymphocytic choriomeningitis virus
Autoimmune Experimental Encephalomyelitis
Immune System Diseases
Coinfection
Phosphoric Monoester Hydrolases
Phosphotransferases
protein phosphatase 5
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Zhang, Y., Blattman, J., Kennedy, N. J., Duong, J., Hguyen, T., Wang, Y., ... Dong, C. (2004). Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature, 430(7001), 793-797. https://doi.org/10.1038/nature02764

Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. / Zhang, Yongliang; Blattman, Joseph; Kennedy, Norman J.; Duong, Julie; Hguyen, Thang; Wang, Ying; Davis, Roger J.; Greenberg, Philip D.; Flavell, Richard A.; Dong, Chen.

In: Nature, Vol. 430, No. 7001, 12.08.2004, p. 793-797.

Research output: Contribution to journalArticle

Zhang, Y, Blattman, J, Kennedy, NJ, Duong, J, Hguyen, T, Wang, Y, Davis, RJ, Greenberg, PD, Flavell, RA & Dong, C 2004, 'Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5', Nature, vol. 430, no. 7001, pp. 793-797. https://doi.org/10.1038/nature02764
Zhang Y, Blattman J, Kennedy NJ, Duong J, Hguyen T, Wang Y et al. Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature. 2004 Aug 12;430(7001):793-797. https://doi.org/10.1038/nature02764
Zhang, Yongliang ; Blattman, Joseph ; Kennedy, Norman J. ; Duong, Julie ; Hguyen, Thang ; Wang, Ying ; Davis, Roger J. ; Greenberg, Philip D. ; Flavell, Richard A. ; Dong, Chen. / Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. In: Nature. 2004 ; Vol. 430, No. 7001. pp. 793-797.
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