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Nat Commun. 2014 Apr 9;5:3618. doi: 10.1038/ncomms4618.

The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck.

Author information

1
Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan.
2
1] Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan [2].
3
1] Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan [2] Department of Medicine, China Medical University, Taichung 40402, Taiwan [3] Division of Rheumatology & Immunology, Department of Internal Medicine, China Medical University Hospital, Taichung 40402, Taiwan [4].
4
1] Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan [2] Faculty of Medicine, National Yang-Ming University, Taipei 11221, Taiwan [3].
5
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
6
1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA [2] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
7
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
8
1] Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan [2] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

JNK pathway-associated phosphatase (JKAP, also known as DUSP22 or JSP-1) is a JNK activator. The in vivo role of JKAP in immune regulation remains unclear. Here we report that JKAP directly inactivates Lck by dephosphorylating tyrosine-394 residue during T-cell receptor (TCR) signalling. JKAP-knockout T cells display enhanced cell proliferation and cytokine production. JKAP-knockout mice show enhanced T-cell-mediated immune responses and are more susceptible to experimental autoimmune encephalomyelitis (EAE). In addition, the recipient mice that are adoptively transferred with JKAP-knockout T cells show exacerbated EAE symptoms. Aged JKAP-knockout mice spontaneously develop inflammation and autoimmunity. Thus, our results indicate that JKAP is an important phosphatase that inactivates Lck in the TCR signalling turn-off stage, leading to suppression of T-cell-mediated immunity and autoimmunity.

PMID:
24714587
DOI:
10.1038/ncomms4618
[Indexed for MEDLINE]

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