PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell Migration Required for Skin Immunity

Although the function of the extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of de...

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Published in:Cell reports (Cambridge) 2020-10, Vol.33 (2), p.108258-108258, Article 108258
Main Authors: Lucas, Erin D., Schafer, Johnathon B., Matsuda, Jennifer, Kraus, Madison, Burchill, Matthew A., Tamburini, Beth A. Jirón
Format: Article
Language:English
Subjects:
actin polymerization
CCR7 signaling
dendritic cell migration
dendritic cell trafficking
dermal dendritic cell
G alpha activation
infection
MAPK signaling
PD-L1 reverse signaling
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Summary:Although the function of the extracellular region of programmed death ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied, little is understood regarding the intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of dendritic cell (DC) migration from the skin to the draining lymph node (dLN). Using a mutant mouse model, we identify a TSS signaling motif within the intracellular domain of PD-L1. The TSS motif proves critical for chemokine-mediated DC migration to the dLN during inflammation. This loss of DC migration, in the PD-L1 TSS mutant, leads to a significant decline in T cell priming when DC trafficking is required for antigen delivery to the dLN. Finally, the TSS motif is required for chemokine receptor signaling downstream of the Gα subunit of the heterotrimeric G protein complex, ERK phosphorylation, and actin polymerization in DCs. [Display omitted] •Loss of PD-L1 impairs dendritic cell (DC) migration from the skin to the lymph node•Mutation of 3 amino acids in the PD-L1 cytoplasmic tail impairs DC migration•PD-L1-dependent DC migration is required for cytotoxic T cell priming•Loss of PD-L1 reverse signaling impedes chemokine receptor signaling Lucas et al. define three residues within the cytoplasmic tail of PD-L1 that are required for proper dendritic cell migration from the skin to the lymph node. These three-amino-acid residues promote chemokine signaling in dendritic cells and productive T cell responses to skin infections.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2020.108258