Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology



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BibTex format

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 = {},
volume = {5},
year = {2014}

RIS format (EndNote, RefMan)

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 -
UR -
VL - 5
ER -