PD-L1-CD80 interactions are required for intracellular signaling necessary for dendritic cell migration.

Abstract

Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration. We show that cis interactions between PD-L1 and CD80 are critical for promoting migration and define specific regions within these proteins necessary for migration. Furthermore, we demonstrate that αPD-L1 significantly impedes DC migration in a B16 melanoma tumor model. Last, we outline how blocking cis PD-L1:CD80 interactions or mutation of the intracellular domain of PD-L1, in an imiquimod-induced murine model of psoriasis, limits DC migration to the lymph node, decreases interleukin-17 production by CD4⁺ T cells in the lymph node, and reduces epidermal thickening. Therefore, PD-L1 and CD80 interactions are important regulators of DC migration to the draining lymph node.