Affordable Access

deepdyve-link
Publisher Website

HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance.

Authors
  • Chuang, Huai-Chia
  • Sheu, Wayne H-H
  • Lin, Yi-Ting
  • Tsai, Ching-Yi
  • Yang, Chia-Yu
  • Cheng, Yu-Jhen
  • Huang, Pau-Yi
  • Li, Ju-Pi
  • Chiu, Li-Li
  • Wang, Xiaohong
  • Xie, Min
  • Schneider, Michael D
  • Tan, Tse-Hua
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Publication Date
Jan 01, 2014
Volume
5
Pages
4602–4602
Identifiers
DOI: 10.1038/ncomms5602
PMID: 25098764
Source
Medline
License
Unknown

Abstract

Proinflammatory cytokines play important roles in insulin resistance. Here we report that mice with a T-cell-specific conditional knockout of HGK (T-HGK cKO) develop systemic inflammation and insulin resistance. This condition is ameliorated by either IL-6 or IL-17 neutralization. HGK directly phosphorylates TRAF2, leading to its lysosomal degradation and subsequent inhibition of IL-6 production. IL-6-overproducing HGK-deficient T cells accumulate 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 insulin resistance in T-HGK cKO mice. In addition, leptin receptor deficiency in T cells inhibits Th17 differentiation and improves the insulin sensitivity in T-HGK cKO mice, which suggests that leptin cooperates with IL-6 to promote Th17 differentiation. Thus, HGK deficiency induces TRAF2/IL-6 upregulation, leading to IL-6/leptin-induced Th17 differentiation in adipose tissue and subsequent insulin resistance. These findings provide insight into the reciprocal regulation between the immune system and the metabolism.

Report this publication

Statistics

Seen <100 times