Bulk RNA Sequencing of sorted LepR+ Sympathetic Associated Perineurial Cells

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 (LepR)-expressing barrier cells which ensheath sympathetic axon bundles in adipose tissues. These LepR-expressing Sympathetic Perineurial Cells (SPCs) produce IL33, a factor for maintenance and recruitment of regulatory T cell (Treg) and eosinophils in AT. Brown adipose tissues (BAT) of mice lacking IL33 in SPCs (SPCIL33cKO) have fewer Treg and eosinophils, resulting in increased BAT inflammation. These SPCIL33cKO mice are more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPCIL33cKO mice have impaired adaptive thermogenesis, and are unresponsive to leptin-induced rescue of metabolic adaptation. We, therefore, identify LepR-expressing SPCs as a source of IL33 which orchestrate an anti-inflammatory environment in BAT, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR+ IL33+SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research. LepR+ cells from the Superior Cervical Ganglia of LepRCRE::Ai32 mice were sorted and sequenced. 3 biological replicates脂肪组织（Adipose Tissues, ATs）受交感神经支配，后者通过脂解与产热过程驱动脂肪量减少。本研究报道了一类表达瘦素受体（leptin receptor, LepR）的免疫调节性屏障细胞，它们包裹脂肪组织内的交感神经轴突束。这类表达LepR的交感神经束膜细胞（Sympathetic Perineurial Cells, SPCs）可合成白介素33（IL33）——该因子能够维持并招募脂肪组织中的调节性T细胞（regulatory T cell, Treg）与嗜酸性粒细胞。在SPC中特异性敲除IL33的小鼠（SPCIL33cKO），其棕色脂肪组织（Brown Adipose Tissues, BAT）内的Treg与嗜酸性粒细胞数量显著减少，进而引发BAT炎症水平升高。此类SPCIL33cKO小鼠更易罹患饮食诱导肥胖，且该表型与进食量无关。进一步研究表明，SPCIL33cKO小鼠的适应性产热功能受损，且无法响应瘦素介导的代谢适应挽救作用。综上，本研究鉴定出表达LepR的SPCs作为IL33的来源，可协同构建棕色脂肪组织内的抗炎微环境，维持交感神经介导的产热功能与体重稳态。表达LepR的IL33阳性SPCs搭建了瘦素信号与体重免疫调控之间的细胞桥梁，整合了此前肥胖研究中相互独立的神经内分泌学与免疫代谢学两大研究领域。本研究对LepR-Cre::Ai32小鼠颈上神经节（Superior Cervical Ganglia）中的LepR阳性细胞进行了分选与测序，共设置3个生物学重复。