MAPK phosphatase 7 regulates T cell differentiation via inhibiting ERK-mediated IL-2 expression

Yongliang Zhang; Kalyan C Nallaparaju; Xin Liu; Huipeng Jiao; Joseph M Reynolds; Zhi-Xin Wang; Chen Dong

doi:10.4049/jimmunol.1402638

MAPK phosphatase 7 regulates T cell differentiation via inhibiting ERK-mediated IL-2 expression

J Immunol. 2015 Apr 1;194(7):3088-95. doi: 10.4049/jimmunol.1402638. Epub 2015 Feb 25.

Authors

Yongliang Zhang¹, Kalyan C Nallaparaju², Xin Liu³, Huipeng Jiao⁴, Joseph M Reynolds⁵, Zhi-Xin Wang², Chen Dong⁶

Affiliations

¹ Immunology Programme, Life Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597; chendong@tsinghua.edu.cn miczy@nus.edu.sg.
² Department of Immunology, Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77030; and.
³ Tsinghua University School of Medicine, Beijing, China 100084.
⁴ Immunology Programme, Life Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597;
⁵ Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597;
⁶ Tsinghua University School of Medicine, Beijing, China 100084 chendong@tsinghua.edu.cn miczy@nus.edu.sg.

Abstract

Members of the MAPK phosphatase (MKP) protein family play critical roles in immune responses through differential regulation of MAPK activation. In this study, we show that MKP7, also known as dual-specificity phosphatase 16, was required for CD4(+) T cell responses in vivo. Mkp7(-/-) CD4(+) T cells exhibited enhanced ERK and JNK activation, and produced increased amount of IL-2 compared with Mkp7(+/+) cells upon activation. Mkp7(-/-) CD4(+) T cells were selectively defective in Th17 differentiation in vitro, which was rescued by blocking IL-2 or inhibition of ERK activation. Furthermore, mice carrying Mkp7(-/-) T cells were deficient in generation of Th17 and T follicular helper cells in vivo, and were resistant to autoimmune experimental encephalomyelitis. Our results thus demonstrate an essential role of MKP7 in effector T cell function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmunity / genetics
Autoimmunity / immunology
Cell Differentiation / genetics*
Dual-Specificity Phosphatases / deficiency
Dual-Specificity Phosphatases / genetics*
Dual-Specificity Phosphatases / metabolism
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / immunology
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Regulation*
Genes, Lethal
Interleukin-2 / genetics*
Interleukin-2 / metabolism
Lymphocyte Activation / immunology
Mice
Mice, Transgenic
Mitogen-Activated Protein Kinase Phosphatases / deficiency
Mitogen-Activated Protein Kinase Phosphatases / genetics*
Mitogen-Activated Protein Kinase Phosphatases / metabolism
Receptors, Antigen, T-Cell / metabolism
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocytes / cytology*
T-Lymphocytes / immunology
T-Lymphocytes / metabolism*
Th17 Cells / cytology
Th17 Cells / immunology
Th17 Cells / metabolism

Substances

Interleukin-2
Receptors, Antigen, T-Cell
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Phosphatases
Dual-Specificity Phosphatases
Dusp16 protein, mouse