Open AccessAdiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling
Author(s) -
Lu Wang,
Yan Luo,
Liping Luo,
Dandan Wu,
Xiaojuan Ding,
Handong Zheng,
Haisha Wu,
Bilian Liu,
Xin Yang,
Floyd Silva,
Chunqing Wang,
Xing Zhang,
Xianyun Zheng,
Jindong Chen,
Jonathan L. Brigman,
Michael A. Mandell,
Zhou Zhang,
Feng Liu,
Xuexian O. Yang,
Meilian Liu
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20191054
Subject(s) - ampk , adiponectin , adipose tissue , endocrinology , adiponectin receptor 1 , medicine , brown adipose tissue , thermogenesis , activator (genetics) , receptor , signal transduction , white adipose tissue , chemistry , phosphorylation , biology , microbiology and biotechnology , protein kinase a , insulin resistance , obesity
ILC2s are present in adipose tissue and play a critical role in regulating adipose thermogenesis. However, the mechanisms underlying the activation of adipose-resident ILC2s remain poorly defined. Here, we show that IL-33, a potent ILC2 activator, stimulates phosphorylation of AMPK at Thr172 via TAK1 in primary ILC2s, which provides a feedback mechanism to inhibit IL-33–induced NF-κB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33–NF-κB signaling. AdipoRon also suppressed cold-induced thermogenic gene expression and energy expenditure in vivo. In contrast, adiponectin deficiency increased the ILC2 fraction and activation, leading to up-regulated thermogenic gene expression in adipose tissue of cold-exposed mice. ILC2 deficiency or blocking ILC2 function by neutralization of the IL-33 receptor with anti-ST2 diminished the suppressive effect of adiponectin on cold-induced adipose thermogenesis and energy expenditure. Taken together, our study reveals that adiponectin is a negative regulator of ILC2 function in adipose tissue via AMPK-mediated negative regulation of IL-33 signaling.