Department of Biology, Bryn Mawr College, Bryn Mawr, PA, United States.
Front Immunol. 2021 Apr 19;12:661974. doi: 10.3389/fimmu.2021.661974. eCollection 2021.
Transmembrane protein engulfment receptors expressed on the surface of phagocytes engage ligands on apoptotic cells and debris to initiate a sequence of events culminating in material internalization and immunologically beneficial outcomes. Engulfment receptors are modular, comprised of functionally independent extracellular ligation domains and cytosolic signaling motifs. Cognate kinases, adaptors, and phosphatases regulate engulfment by controlling the degree of receptor activation in phagocyte plasma membranes, thus acting as receptor-proximal signaling modules. Here, we review recent efforts to reprogram phagocytes using modular synthetic receptors composed of antibody-based extracellular domains fused to engulfment receptor signaling domains. To aid the development of new phagocyte reprogramming methods, we then define the kinases, adaptors, and phosphatases that regulate a conserved family of engulfment receptors. Finally, we discuss current challenges and opportunities for the field.
吞噬细胞表面表达的跨膜蛋白吞噬受体与凋亡细胞和碎片上的配体结合，启动一系列事件，最终导致物质内化和免疫有益的结果。吞噬受体是模块化的，由功能上独立的细胞外连接域和胞质信号基序组成。同源激酶、衔接蛋白和磷酸酶通过控制吞噬细胞质膜中受体的激活程度来调节吞噬作用，因此作为受体近端信号模块发挥作用。在这里，我们综述了使用基于抗体的细胞外结构域与吞噬受体信号结构域融合而成的模块化合成受体来重新编程吞噬细胞的最新进展。为了帮助开发新的吞噬细胞重编程方法，我们随后定义了调节一组保守的吞噬受体的激酶、衔接蛋白和磷酸酶。最后，我们讨论了该领域当前的挑战和机遇。
