英国牛津大学Ana I. Domingos研究团队发现，具有免疫调节作用的瘦素受体⁺交感神经周围屏障细胞通过促进棕色脂肪组织产热来预防肥胖症。这一研究成果于2023年12月12日在线发表在国际学术期刊《免疫》上。

研究人员报告了存在于小鼠和人体内的一群免疫调节瘦素受体阳性（LepR⁺）交感神经周围屏障细胞（SPC），它们独特地共同表达Lepr和白细胞介素-33（Il33），并包被交感神经轴突束。在SPC中缺乏IL-33（SPC^ΔIl33）的小鼠棕色脂肪组织（BAT）中，调节性T（Treg）细胞和嗜酸性粒细胞较少，导致BAT炎症加剧。SPC^ΔIl33小鼠更容易受到饮食诱发肥胖的影响，这与食物摄入量无关。

此外，SPC^ΔIl33小鼠的适应性产热功能受损，对瘦素诱导的代谢适应性拯救反应迟钝。因此，研究人员将LepR⁺ SPC鉴定为IL-33的来源，IL-33可协调BAT的抗炎环境，保护交感神经介导的产热和体重平衡。LepR⁺IL-33⁺ SPC提供了瘦素和体重免疫调节之间的细胞联系，并将神经内分泌学和免疫代谢学这两个以前互不关联的肥胖研究领域统一起来。

据了解，脂肪组织受交感神经支配，交感神经通过脂肪分解和产热来减少脂肪量。

附：英文原文

Title: Immunomodulatory leptin receptor+ sympathetic perineurial barrier cells protect against obesity by facilitating brown adipose tissue thermogenesis

Author: Emma R. Haberman, Gitalee Sarker, Bernardo A. Arús, Karin A. Ziegler, Sandro Meunier, Noelia Martínez-Sánchez, Elika Freibergerová, Sinem Yilmaz-zcan, Iara Fernández-González, Chloe Zentai, Conan J.O. O’Brien, David E. Grainger, Davi Sidarta-Oliveira, Svetoslav Chakarov, Andrea Raimondi, Matteo Iannacone, Stefan Engelhardt, Miguel López, Florent Ginhoux, Ana I. Domingos

Issue&Volume: 2023-12-12

Abstract: Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reductionof fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatoryleptin receptor-positive (LepR+) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquelyco-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33in SPCs (SPCΔIl33) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BATinflammation. SPCΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake.Furthermore, SPCΔIl33 mice had impaired adaptive thermogenesis and were unresponsive to leptin-inducedrescue 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 fieldsof obesity research.

DOI: 10.1016/j.immuni.2023.11.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00488-0