氧化磷酸化選擇性地調節組織巨噬細胞穩態

西班牙卡洛斯三世國家心血管研究中心David Sancho等研究人員合作發現，氧化磷酸化選擇性地調節組織巨噬細胞穩態。這一研究成果于2023年2月3日在線發表在國際學術期刊《免疫》上。

通過分析人類和小鼠的RNA-seq數據，研究人員確定氧化磷酸化（OXPHOS）是不同器官組織巨噬細胞（TMF）在穩態中的最大差異過程。通過Tfam缺失來損害TMF中的OXPHOS對TMF種群有不同的影響。Tfam缺失導致肺泡巨噬細胞（AM）減少，這是由于脂質處理能力受損，導致膽固醇含量增加和細胞應激，進而使得體內細胞周期阻滯。在肥胖中，Tfam敲除選擇性地去除促炎的脂質處理白色脂肪組織巨噬細胞（WAT-MF），從而預防胰島素抵抗和肝穩態。因此，OXPHOS而非糖酵解能夠區分TMF群體，并且對于維持具有高脂處理活性的TMF至關重要，包括促炎的WAT-MF。這可以提供一種選擇性的靶向治療工具。

據悉，體外研究已將OXPHOS與抗炎巨噬細胞聯系起來，而促炎巨噬細胞依賴于糖酵解。然而，TMF中實現其穩態活動的代謝需求尚不完全清楚。

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