Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan.
Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan.
复制标题
程序性细胞死亡 1 途径的减弱会增加酵母聚糖诱导的巨噬细胞的 M1 极化
DOI：
10.1038/cddis.2016.33
复制
发表时间：
2016-02-25
影响因子：
9
通讯作者：
Tian Y
中科院分区：
文献类型：
--
作者：
Chen W;Wang J;Jia L;Liu J;Tian Y
程序性细胞死亡-1（PD-1）是CD 28超家族的成员，在与其2种配体PD-L1和PD-L2相互作用时传递负信号。我们评估了PD-1通路对调节巨噬细胞极化的贡献，巨噬细胞促进酵母多糖诱导的炎症。我们发现，PD-1−/−小鼠发生了强烈的腹膜炎，M1巨噬细胞浸润更丰富，伴随着更高水平的促炎症因子，特别是单核细胞趋化蛋白-1（MCP-1），与野生型对照相比，离体和体外。我们的研究结果表明PD-1缺陷通过增强p-STAT 1/p-NF-κB p65的表达和下调p-STAT 6促进巨噬细胞的M1而不是M2极化。我们发现，PD-1接合后酵母聚糖刺激可能主要减弱PD-1受体/配体中酪氨酸残基的磷酸化和SHP-2向PD-1受体/配体的募集，导致M1型细胞因子产生的减少。
Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We assessed the contribution of the PD-1 pathway to regulating the polarization of macrophages that promote inflammation induced by zymosan. We found that PD-1−/− mice developed robust peritonitis with more abundant infiltration of M1 macrophages, accompanied by higher levels of pro-inflammation factors, especially monocyte chemotactic protein-1 (MCP-1) compared with wild-type controls ex vivo and in vitro. Our results indicated that PD-1 deficiency promotes M1 rather than M2 polarization of macrophages by enhancing the expression of p-STAT1/p-NF-κB p65 and downregulating p-STAT6. We found that PD-1 engagement followed by zymosan stimulation might primarily attenuate the phosphorylation of tyrosine residue in PD-1 receptor/ligand and the recruitment of SHP-2 to PD-1 receptor/ligand, leading to the reduction of M1 type cytokine production.