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

doi:10.1038/ncomms4618

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 journal › Journal Article › peer-review

117 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 language	English
Article number	3618
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4618
State	Published - 09 04 2014
Externally published	Yes

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

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.",

author = "Li, {Ju Pi} and Yang, {Chia Yu} and Chuang, {Huai Chia} and Lan, {Joung Liang} and Chen, {Der Yuan} and Chen, {Yi Ming} and Xiaohong Wang and Chen, {Alice J.} and Belmont, {John W.} and Tan, {Tse Hua}",

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day = "9",

doi = "10.1038/ncomms4618",

language = "英语",

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journal = "Nature Communications",

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T1 - The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck

AU - Li, Ju Pi

AU - Yang, Chia Yu

AU - Chuang, Huai Chia

AU - Lan, Joung Liang

AU - Chen, Der Yuan

AU - Chen, Yi Ming

AU - Wang, Xiaohong

AU - Chen, Alice J.

AU - Belmont, John W.

AU - Tan, Tse Hua

PY - 2014/4/9

Y1 - 2014/4/9

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

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

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