College of Life Sciences, Shaanxi Normal University, Xi'an, China.
PLoS Genet. 2021 Dec 3;17(12):e1009947. doi: 10.1371/journal.pgen.1009947. eCollection 2021 Dec.
Efferocytosis is the process by which phagocytes recognize, engulf, and digest (or clear) apoptotic cells during development. Impaired efferocytosis is associated with developmental defects and autoimmune diseases. In Drosophila melanogaster, recognition of apoptotic cells requires phagocyte surface receptors, including the scavenger receptor CD36-related protein, Croquemort (Crq, encoded by crq). In fact, Crq expression is upregulated in the presence of apoptotic cells, as well as in response to excessive apoptosis. Here, we identified a novel gene bfc (booster for croquemort), which plays a role in efferocytosis, specifically the regulation of the crq expression. We found that Bfc protein interacts with the zinc finger domain of the GATA transcription factor Serpent (Srp), to enhance its direct binding to the crq promoter; thus, they function together in regulating crq expression and efferocytosis. Overall, we show that Bfc serves as a Srp co-factor to upregulate the transcription of the crq encoded receptor, and consequently boosts macrophage efferocytosis in response to excessive apoptosis. Therefore, this study clarifies how phagocytes integrate apoptotic cell signals to mediate efferocytosis.
噬作用是指在发育过程中，吞噬细胞识别、吞噬和消化（或清除）凋亡细胞的过程。噬作用受损与发育缺陷和自身免疫性疾病有关。在黑腹果蝇中，吞噬细胞表面受体（包括清道夫受体 CD36 相关蛋白 Croquemort（Crq，由 crq 编码））识别凋亡细胞。事实上，Crq 的表达在存在凋亡细胞以及对凋亡过度的反应中上调。在这里，我们鉴定了一个新基因 bfc（Croquemort 的增强子），它在噬作用中起作用，特别是调节 crq 的表达。我们发现 Bfc 蛋白与 GATA 转录因子 Serpent（Srp）的锌指结构域相互作用，以增强其直接结合到 crq 启动子上；因此，它们共同作用于调节 crq 的表达和噬作用。总的来说，我们表明 Bfc 作为 Srp 的共因子，上调编码受体的 crq 的转录，从而增强巨噬细胞对过度凋亡的噬作用。因此，本研究阐明了吞噬细胞如何整合凋亡细胞信号来介导噬作用。
