The obesity-induced adipokine sST2 exacerbates adipose T_reg and ILC2 depletion and promotes insulin resistance.

ABSTRACT: Depletion of fat-resident regulatory T cells (T_regs) and group 2 innate lymphoid cells (ILC2s) has been causally linked to obesity-associated insulin resistance. However, the molecular nature of the pathogenic signals suppress adipose T_regs and ILC2s in obesity remains unknown. Here, we identified the soluble isoform of interleukin (IL)-33 receptor ST2 (sST2) as an obesity-induced adipokine that attenuates IL-33 signaling and disrupts T_reg/ILC2 homeostasis in adipose tissue, thereby exacerbates obesity-associated insulin resistance in mice. We demonstrated sST2 is a target of TNFα signaling in adipocytes that is countered by Zbtb7b. Fat-specific ablation of Zbtb7b augments adipose sST2 gene expression, leading to diminished fat-resident T_regs/ILC

SUBMITTER: Zhao XY 

PROVIDER: S-EPMC7220368 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature