Krause Will, King Diane, Horsley Valerie
Dept. of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA.
SunnyCrest Bioinformatics, Flemington, New Jersey, USA.
bioRxiv. 2024 Aug 13:2024.08.12.607219. doi: 10.1101/2024.08.12.607219.
Defects in apoptotic cell clearance, or efferocytosis, can cause inflammatory diseases and prevent tissue repair due in part to inducing a pro-repair transcriptional program in phagocytic cells like macrophages. While the cellular machinery and metabolic pathways involved in efferocytosis have been characterized, the precise efferocytic response of macrophages is dependent on the identity and macromolecular cues of apoptotic cells, and the complex tissue microenvironment in which efferocytosis occurs. Here, we find that macrophages undergoing active efferocytosis in mid-stage mouse skin wounds in vivo display a pro-repair gene program, while efferocytosis of apoptotic skin fibroblasts in vitro also induces an inflammatory transcription response. These data provide a resource for understanding how the skin wound environment influences macrophage efferocytosis and will be useful for future investigations that define the role of efferocytosis during tissue repair.
凋亡细胞清除（即胞葬作用）缺陷可导致炎症性疾病，并阻碍组织修复，部分原因是它会在巨噬细胞等吞噬细胞中诱导促修复转录程序。虽然胞葬作用所涉及的细胞机制和代谢途径已得到明确，但巨噬细胞精确的胞葬反应取决于凋亡细胞的特性和大分子信号，以及胞葬作用发生的复杂组织微环境。在这里，我们发现，在体内中期小鼠皮肤伤口中进行活跃胞葬作用的巨噬细胞表现出促修复基因程序，而体外凋亡皮肤成纤维细胞的胞葬作用也会诱导炎症转录反应。这些数据为理解皮肤伤口环境如何影响巨噬细胞胞葬作用提供了资源，将有助于未来确定胞葬作用在组织修复过程中作用的研究。
