Olfactory ensheathing cells (OECs) have been shown to be a leading candidate in cell therapies for central nervous system (CNS) injuries and neurodegenerative diseases. Rapid clearance of neuron debris can promote neuronal survival and axonal regeneration in CNS injuries and neurodegenerative diseases. The phagocytic removal of neuron debris by OECs has been shown to contribute to neuronal outgrowth. However, the precise molecular and cellular mechanisms of phagocytic removal of neuron debris by OECs have not been explored. In this study, we found that OECs secreted anti-inflammatory cytokine transforming growth factor β1 (TGF-β1) during the phagocytic removal of neuron debris. TGF-β1 enhanced phagocytic activity of OECs through regulating integrin/MFG-E8 signaling pathway. In addition, TGF-β1 shifted OECs towards a flattened shape with increased cellular area, which might also be involved in the enhancement of phagocytic activity of OECs. Furthermore, the removal of neuron debris by OECs affected neuronal survival and outgrowth. TGF-β1 enhanced the clearance of neuron debris by OECs and increased neuronal survival. These results reveal the role and mechanism of TGF-β1 in enhancing the phagocytic activity of OECs, which will update the understanding of phagocytosis of OECs and improve the therapeutic use of OECs in CNS injuries and neurodegenerative diseases.

嗅鞘细胞（OECs）已被证明是中枢神经系统（CNS）损伤和神经退行性疾病的细胞疗法的领先候选者。快速清除神经元碎片可以促进中枢神经系统损伤和神经退行性疾病中神经元的存活和轴突再生。OECs吞噬去除神经元碎片已被证明有助于神经元的生长。但是，尚未探索通过OEC吞噬清除神经元碎片的精确分子和细胞机制。在这项研究中，我们发现OEC在吞噬去除神经元碎片的过程中分泌了抗炎细胞因子转化生长因子β1（TGF-β1）。TGF-β1通过调节整联蛋白/ MFG-E8信号通路增强了OEC的吞噬活性。此外，TGF-β1使OECs趋向于扁平状，细胞面积增加，这也可能与增强OEC的吞噬活性有关。此外，OEC去除神经元碎片会影响神经元的存活和生长。TGF-β1增强了OECs对神经元碎片的清除作用，并提高了神经元存活率。这些结果揭示了TGF-β1在增强OEC的吞噬活性中的作用和机制，这将更新对OEC的吞噬作用的理解，并改善OEC在中枢神经系统损伤和神经退行性疾病中的治疗用途。