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

Author

Listed:
  • 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
    China Medical University
    China Medical University Hospital)

  • Der-Yuan Chen

    (Immunology, and Rheumatology, Taichung Veterans General Hospital
    Faculty of Medicine, National Yang-Ming University)

  • Yi-Ming Chen

    (Immunology, and Rheumatology, Taichung Veterans General Hospital
    Faculty of Medicine, National Yang-Ming University)

  • Xiaohong Wang

    (Baylor College of Medicine)

  • Alice J. Chen

    (Baylor College of Medicine
    Baylor College of Medicine)

  • John W. Belmont

    (Baylor College of Medicine)

  • Tse-Hua Tan

    (Immunology Research Center, National Health Research Institutes
    Baylor College of Medicine)

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.

Suggested Citation

  • Ju-Pi Li & Chia-Yu Yang & Huai-Chia Chuang & Joung-Liang Lan & Der-Yuan Chen & Yi-Ming Chen & Xiaohong Wang & Alice J. Chen & John W. Belmont & Tse-Hua Tan, 2014. "The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4618
    DOI: 10.1038/ncomms4618
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    Cited by:

    1. Ying-Chun Shih & Hsueh-Fen Chen & Chia-Ying Wu & Yi-Ru Ciou & Chia-Wen Wang & Huai-Chia Chuang & Tse-Hua Tan, 2024. "The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Chenxu Ge & Jun Tan & Xianling Dai & Qin Kuang & Shaoyu Zhong & Lili Lai & Chao Yi & Yan Sun & Jing Luo & Chufeng Zhang & Liancai Zhu & Bochu Wang & Minxuan Xu, 2022. "Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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