PD-L1-CD80 Interactions Are Required for Intracellular Signaling Necessary for Dendritic Cell Migration

Overview

Journal Sci Adv

Date 2025 Jan 29

PMID 39879305

Authors

Uma Kantheti

Tadg S Forward

Erin D Lucas

Johnathon B Schafer

Pierce J Tamburini

Matthew A Burchill

Beth Ann Jiron Tamburini

Affiliations

Soon will be listed here.

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.

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