Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Mol Cells. 2019 Jan 31;42(1):1-7. doi: 10.14348/molcells.2018.0419. Epub 2019 Jan 2.
Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.
巨噬细胞是一种重要的先天免疫细胞，不仅能引发炎症反应，还能在组织修复和抗炎反应中发挥作用。因此，调节巨噬细胞的活性对于维持免疫稳态至关重要。TYRO3、AXL 和 MER 是整合膜蛋白，构成了 TAM 家族受体酪氨酸激酶（RTKs）。越来越多的证据表明，TAM 家族受体通过调节巨噬细胞的功能在抗炎反应中发挥重要作用。首先，巨噬细胞可以通过表达在巨噬细胞上的 TAM 家族受体与附着在凋亡体上的配体之间的相互作用来识别凋亡体。如果没有 TAM 信号，巨噬细胞就无法清除凋亡细胞，导致免疫细胞过度激活而引发广泛的炎症。其次，TAM 信号可以通过特定的模式识别受体和细胞因子受体来减弱炎症途径，从而防止巨噬细胞的慢性激活。第三，TAM 信号可以诱导自噬，这是抑制巨噬细胞中 NLRP3 炎性小体激活的重要机制。第四，TAM 信号可以抑制 M1 巨噬细胞的极化。在这篇综述中，我们将重点讨论 TAM 家族 RTKs 如何调节与抗炎反应相关的巨噬细胞功能的机制。我们还将讨论几种与 TAM 信号相关的人类疾病和靶向 TAM 信号的潜在治疗策略。
