PD-1 的协同抑制
中文名称
通路描述
程序性细胞死亡蛋白 1（PD-1）是一种关键的抑制性受体，调节 T 细胞受体（TCR）信号并维持免疫稳态。PD-1 通过直接抑制由共刺激信号（如 CD28）增强的早期激活事件，以及间接减少白细胞介素 -2（IL-2）的产生来发挥其抑制作用，而 IL-2 对于 T 细胞的增殖和生存至关重要。当 PD-1 被配体结合时，它抑制关键生存和分化因子的表达，如 Bcl-xL，并下调介导效应 T 细胞功能的转录因子，包括 GATA-3、T-bet 和 Eomes。在机制上，PD-1 招募酪氨酸磷酸酶 SHP-1 和 SHP-2 至免疫突触，导致关键信号分子如 CD3-zeta 链、PI3K 和 AKT的去磷酸化，从而减弱 TCR 信号并抑制 T 细胞激活和功能（Keir et al. 2008）。
英文描述
Co-inhibition by PD-1 Programmed cell death protein 1 (PD-1) is a crucial inhibitory receptor that regulates T cell receptor (TCR) signaling and plays a vital role in maintaining immune homeostasis. PD-1 exerts its suppressive effects both directly, by inhibiting early activation events that are otherwise enhanced by co-stimulatory signals like CD28, and indirectly, by reducing interleukin-2 (IL-2) production, which is essential for T cell proliferation and survival. Upon ligation, PD-1 inhibits the expression of key survival and differentiation factors, such as Bcl-xL, and downregulates transcription factors that are central to effector T cell function, including GATA-3, T-bet, and Eomes. Mechanistically, PD-1 recruits the tyrosine phosphatases SHP-1 and SHP-2 to the immune synapse, leading to the dephosphorylation of critical signaling molecules like the CD3-zeta chain, PI3K, and AKT, thereby attenuating TCR signaling and inhibiting T cell activation and function (Keir et al. 2008).
所含基因
17 个基因