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

Abstract

While the function of 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 small intracellular domain of PD-L1. Here, we outline a major role for PD-L1 intracellular signaling in the control of DC migration from the skin to the draining lymph node (dLN). Using a mutant mouse model we identified a TSS signaling motif within the intracellular domain of PD-L1. While loss of the TSS motif had no impact on PD-L1 expression, this motif proved critical for chemokine mediated DC migration to the dLN during inflammation. The loss of DC chemokine mediated migration, in the PD-L1 TSS mutant, led to a significant decline in T cell priming when DC trafficking was required for antigen delivery to the dLN. Finally, the TSS motif was required for ERK phosphorylation and actin polymerization in DCs treated with chemokine.