氧化磷酸化选择性地调节组织巨噬细胞稳态

西班牙卡洛斯三世国家心血管研究中心David Sancho等研究人员合作发现，氧化磷酸化选择性地调节组织巨噬细胞稳态。这一研究成果于2023年2月3日在线发表在国际学术期刊《免疫》上。

通过分析人类和小鼠的RNA-seq数据，研究人员确定氧化磷酸化（OXPHOS）是不同器官组织巨噬细胞（TMF）在稳态中的最大差异过程。通过Tfam缺失来损害TMF中的OXPHOS对TMF种群有不同的影响。Tfam缺失导致肺泡巨噬细胞（AM）减少，这是由于脂质处理能力受损，导致胆固醇含量增加和细胞应激，进而使得体内细胞周期阻滞。在肥胖中，Tfam敲除选择性地去除促炎的脂质处理白色脂肪组织巨噬细胞（WAT-MF），从而预防胰岛素抵抗和肝稳态。因此，OXPHOS而非糖酵解能够区分TMF群体，并且对于维持具有高脂处理活性的TMF至关重要，包括促炎的WAT-MF。这可以提供一种选择性的靶向治疗工具。

据悉，体外研究已将OXPHOS与抗炎巨噬细胞联系起来，而促炎巨噬细胞依赖于糖酵解。然而，TMF中实现其稳态活动的代谢需求尚不完全清楚。

附：英文原文

Title: Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis

Author: Stefanie K. Wculek, Ignacio Heras-Murillo, Annalaura Mastrangelo, Diego Maanes, Miguel Galán, Verónica Miguel, Andrea Curtabbi, Coral Barbas, Navdeep S. Chandel, José Antonio Enríquez, Santiago Lamas, David Sancho

Issue&Volume: 2023-02-03

Abstract: In vitro studies have associated oxidative phosphorylation (OXPHOS) with anti-inflammatorymacrophages, whereas pro-inflammatory macrophages rely on glycolysis. However, themetabolic needs of macrophages in tissues (TMFs) to fulfill their homeostatic activitiesare incompletely understood. Here, we identified OXPHOS as the highest discriminatingprocess among TMFs from different organs in homeostasis by analysis of RNA-seq datain both humans and mice. Impairing OXPHOS in TMFs via Tfam deletion differentially affected TMF populations. Tfam deletion resulted in reduction of alveolar macrophages (AMs) due to impaired lipid-handlingcapacity, leading to increased cholesterol content and cellular stress, causing cell-cyclearrest in vivo. In obesity, Tfam depletion selectively ablated pro-inflammatory lipid-handling white adipose tissuemacrophages (WAT-MFs), thus preventing insulin resistance and hepatosteatosis. Hence,OXPHOS, rather than glycolysis, distinguishes TMF populations and is critical forthe maintenance of TMFs with a high lipid-handling activity, including pro-inflammatoryWAT-MFs. This could provide a selective therapeutic targeting tool.

DOI: 10.1016/j.immuni.2023.01.011

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00021-3