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

Ju-Pi Li, Chia-Yu Yang, Huai-Chia Chuang, Joung-Liang Lan, Chen Der-Yuan, Yi-Ming Chen, Xiaohong Wang, Alice J. Chen, John W. Belmont and Tse-Hua Tan ()
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Ju-Pi Li: Immunology Research Center, National Health Research Institutes
Chia-Yu Yang: Immunology Research Center, National Health Research Institutes
Huai-Chia Chuang: Immunology Research Center, National Health Research Institutes
Joung-Liang Lan: Immunology, and Rheumatology, Taichung Veterans General Hospital
Chen Der-Yuan: Immunology, and Rheumatology, Taichung Veterans General Hospital
Yi-Ming Chen: Immunology, and Rheumatology, Taichung Veterans General Hospital
Xiaohong Wang: Baylor College of Medicine
Alice J. Chen: Baylor College of Medicine
John W. Belmont: Baylor College of Medicine
Tse-Hua Tan: Immunology Research Center, National Health Research Institutes

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4618

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