CD80
细胞生物学
效应器
免疫系统
T细胞
PI3K/AKT/mTOR通路
癌症研究
MAPK/ERK通路
生物
CD86
蛋白激酶B
信号转导
化学
免疫学
体外
CD40
细胞毒性T细胞
生物化学
作者
Wenji Piao,Lushen Li,Vikas Saxena,Jegan Iyyathurai,Ram Lakhan,Yigang Zhang,Isadora T. Lape,Christina Paluskievicz,Keli L. Hippen,Young Lee,Emma Silverman,Marina W. Shirkey,Leonardo V. Riella,Bruce R. Blazar,Jonathan S. Bromberg
标识
DOI:10.1038/s41467-022-29930-0
摘要
Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation.
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