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

123 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms4618

Cite this

@article{0b8e7bef3d5e4252b4877a62a6896ab3,

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\}",

year = "2014",

month = apr,

day = "9",

doi = "10.1038/ncomms4618",

language = "英语",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/84898427825

U2 - 10.1038/ncomms4618

DO - 10.1038/ncomms4618

M3 - 文章

C2 - 24714587

AN - SCOPUS:84898427825

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 3618

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this