PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration
| Autor: | 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 |
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| Rok vydání: | 2021 |
| Předmět: |
Multidisciplinary
Programmed Cell Death 1 Receptor Transendothelial and Transepithelial Migration General Physics and Astronomy Endothelial Cells Vascular Cell Adhesion Molecule-1 hemic and immune systems chemical and pharmacologic phenomena General Chemistry Ligands T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology B7-H1 Antigen Phosphatidylinositol 3-Kinases B7-1 Antigen |
| Zdroj: | Nature communications. 13(1) |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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