UNC Neuroscience Center, University of North Carolina-CH, Chapel Hill, NC, United States.
UNC Neuroscience Center, University of North Carolina-CH, Chapel Hill, NC, United States; UNC Department of Microbiology & Immunology, University of North Carolina-CH, Chapel Hill, NC, United States; UNC Integrative Program for Biological & Genome Sciences, University of North Carolina-CH, Chapel Hill, NC, United States.
Int Rev Cell Mol Biol. 2021;361:165-210. doi: 10.1016/bs.ircmb.2021.02.002. Epub 2021 May 10.
Three structurally related tyrosine receptor cell surface kinases, Tyro3, Axl, and Mertk (TAM) have been recognized to modulate immune function, tissue homeostasis, cardiovasculature, and cancer. The TAM receptor family appears to operate in adult mammals across multiple cell types, suggesting both widespread and specific regulation of cell functions and immune niches. TAM family members regulate tissue homeostasis by monitoring the presence of phosphatidylserine expressed on stressed or apoptotic cells. The detection of phosphatidylserine on apoptotic cells requires intermediary molecules that opsonize the dying cells and tether them to TAM receptors on phagocytes. This complex promotes the engulfment of apoptotic cells, also known as efferocytosis, that leads to the resolution of inflammation and tissue healing. The immune mechanisms dictating these processes appear to fall upon specific family members or may involve a complex of different receptors acting cooperatively to resolve and repair damaged tissues. Here, we focus on the role of TAM receptors in triggering efferocytosis and its consequences in the regulation of immune responses in the context of inflammation and cancer.
三种结构相关的酪氨酸受体细胞表面激酶，即 Tyro3、Axl 和 Mertk（TAM），已被认为可以调节免疫功能、组织稳态、心血管系统和癌症。TAM 受体家族似乎在成年哺乳动物的多种细胞类型中发挥作用，这表明对细胞功能和免疫生态位进行了广泛和特定的调节。TAM 家族成员通过监测应激或凋亡细胞上表达的磷脂酰丝氨酸来调节组织稳态。凋亡细胞上磷脂酰丝氨酸的检测需要中介分子将垂死的细胞调理并与吞噬细胞上的 TAM 受体结合。这种复合物促进了凋亡细胞的吞噬作用，也称为噬作用，导致炎症的解决和组织的修复。决定这些过程的免疫机制似乎取决于特定的家族成员，或者可能涉及不同受体的复合物协同作用以解决和修复受损组织。在这里，我们重点关注 TAM 受体在触发噬作用及其在炎症和癌症背景下调节免疫反应中的后果的作用。
