| First Author | Wang L | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 2 | PubMed ID | 33104171 |
| Mgi Jnum | J:307784 | Mgi Id | MGI:6509803 |
| Doi | 10.1084/jem.20191054 | Citation | Wang L, et al. (2021) Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling. J Exp Med 218(2) |
| abstractText | 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-kappaB activation and IL-13 production. Treating ILC2s with adiponectin or an adiponectin receptor agonist (AdipoRon) activated AMPK and decreased IL-33-NF-kappaB 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. |
