Tissue-resident macrophages (TRMs) are heterogeneous cell populations found throughout the body. Depending on their location, they perform diverse functions maintaining tissue homeostasis and providing immune surveillance. To survive and function within, TRMs adapt metabolically to the distinct microenvironments. However, little is known about the metabolic signatures of TRMs. The thymus provides a nurturing milieu for developing thymocytes yet efficiently removes those that fail the selection, relying on the resident thymic macrophages (TMφs). This study harnesses multiomics analyses to characterize TMφs and unveils their metabolic features. We find that the pentose phosphate pathway (PPP) is preferentially activated in TMφs, responding to the reduction-oxidation demands associated with the efferocytosis of dying thymocytes. The blockade of PPP in Mφs leads to decreased efferocytosis, which can be rescued by reactive oxygen species (ROS) scavengers. Our study reveals the key role of the PPP in TMφs and underscores the importance of metabolic adaptation in supporting Mφ efferocytosis.

组织驻留巨噬细胞 (TRM) 是遍布全身的异质细胞群。根据它们的位置，它们执行不同的功能来维持组织稳态和提供免疫监视。为了在其中生存和发挥作用，TRM 在代谢上适应不同的微环境。然而，人们对 TRM 的代谢特征知之甚少。胸腺为胸腺细胞的发育提供了一个培育环境，但依赖于常驻的胸腺巨噬细胞 (TMφs) 有效地去除了那些未能通过选择的胸腺细胞。本研究利用多组学分析来表征 TMφs 并揭示其代谢特征。我们发现戊糖磷酸途径 (PPP) 在 TMφs 中优先被激活，以响应与垂死胸腺细胞的胞吐作用相关的还原-氧化需求。Mφs 中 PPP 的阻断导致细胞增多症减少，这可以通过活性氧 (ROS) 清除剂来挽救。我们的研究揭示了 PPP 在 TMφs 中的关键作用，并强调了代谢适应在支持 Mφ efferocytosis 中的重要性。