Imperial College London
Alternate

Emeritus ProfessorMichaelSchneider

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor in Cardiology
 
 
 
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Contact

 

+44 (0)013 34621727m.d.schneider Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chuang:2014:10.1038/ncomms5602,
author = {Chuang, H-C and Sheu, WH-H and Lin, Y-T and Tsai, C-Y and Yang, C-Y and Cheng, Y-J and Huang, P-Y and Li, J-P and Chiu, L-L and Wang, X and Xie, M and Schneider, MD and Tan, T-H},
doi = {10.1038/ncomms5602},
journal = {Nature Communications},
title = {HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance},
url = {http://dx.doi.org/10.1038/ncomms5602},
volume = {5},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Proinflammatory cytokines play important roles in insulin resistance. Here we report thatmice with a T-cell-specific conditional knockout of HGK (T-HGK cKO) develop systemicinflammation and insulin resistance. This condition is ameliorated by either IL-6 or IL-17neutralization. HGK directly phosphorylates TRAF2, leading to its lysosomal degradationand subsequent inhibition of IL-6 production. IL-6-overproducing HGK-deficient T cellsaccumulate in adipose tissue and further differentiate into IL-6/IL-17 double-positive cells.Moreover, CCL20 neutralization or CCR6 deficiency reduces the Th17 population or insulinresistance in T-HGK cKO mice. In addition, leptin receptor deficiency in T cells inhibits Th17differentiation and improves the insulin sensitivity in T-HGK cKO mice, which suggests thatleptin cooperates with IL-6 to promote Th17 differentiation. Thus, HGK deficiency inducesTRAF2/IL-6 upregulation, leading to IL-6/leptin-induced Th17 differentiation in adiposetissue and subsequent insulin resistance. These findings provide insight into the reciprocalregulation between the immune system and the metabolism.
AU  - Chuang,H-C
AU  - Sheu,WH-H
AU  - Lin,Y-T
AU  - Tsai,C-Y
AU  - Yang,C-Y
AU  - Cheng,Y-J
AU  - Huang,P-Y
AU  - Li,J-P
AU  - Chiu,L-L
AU  - Wang,X
AU  - Xie,M
AU  - Schneider,MD
AU  - Tan,T-H
DO  - 10.1038/ncomms5602
PY  - 2014///
SN  - 2041-1723
TI  - HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms5602
UR  - http://hdl.handle.net/10044/1/26825
VL  - 5
ER  -
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