| First Author | Haberman ER | Year | 2024 |
| Journal | Immunity | Volume | 57 |
| Issue | 1 | Pages | 141-152.e5 |
| PubMed ID | 38091996 | Mgi Jnum | J:349260 |
| Mgi Id | MGI:7574083 | Doi | 10.1016/j.immuni.2023.11.006 |
| Citation | Haberman ER, et al. (2024) Immunomodulatory leptin receptor(+) sympathetic perineurial barrier cells protect against obesity by facilitating brown adipose tissue thermogenesis. Immunity 57(1):141-152.e5 |
| abstractText | Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reduction of fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatory leptin receptor-positive (LepR(+)) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquely co-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33 in SPCs (SPC(DeltaIl33)) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BAT inflammation. SPC(DeltaIl33) mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPC(DeltaIl33) mice had impaired adaptive thermogenesis and were unresponsive to leptin-induced rescue of metabolic adaptation. We therefore identify LepR(+) SPCs as a source of IL-33, which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR(+)IL-33(+) SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research. |
