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, Der Yuan Chen, Yi Ming Chen, Xiaohong Wang, Alice J. Chen, John W. Belmont, Tse Hua Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

107 Scopus citations

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.

Original languageEnglish
Article number3618
JournalNature Communications
Volume5
DOIs
StatePublished - 09 04 2014
Externally publishedYes

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