PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration

被引：0
作者：
Wenji Piao
Lushen Li
Vikas Saxena
Jegan Iyyathurai
Ram Lakhan
Yigang Zhang
Isadora Tadeval Lape
Christina Paluskievicz
Keli L. Hippen
Young Lee
Emma Silverman
Marina W. Shirkey
Leonardo V. Riella
Bruce R. Blazar
Jonathan S. Bromberg
机构：
[1] Center for Vascular and Inflammatory Diseases,Department of Surgery
[2] University of Maryland School of Medicine,Department of Microbiology and Immunology
[3] University of Maryland School of Medicine,undefined
[4] Division of Blood & Marrow Transplant & Cellular Therapy,undefined
[5] Department of Pediatrics,undefined
[6] University of Minnesota Cancer Center,undefined
[7] Center for Transplantation Sciences,undefined
[8] Department of Surgery,undefined
[9] Massachusetts General Hospital,undefined
[10] Boston,undefined
[11] Massachusetts,undefined
[12] University of Maryland School of Medicine,undefined
来源：
Nature Communications | / 13卷
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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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