Abstract
Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) interactions are critical for dampening the immune response to both self and foreign antigens. The signaling of PD-L1 via its cytoplasmic domain, rather than through its interactions with PD-1 via the extracellular domain, has been termed PD-L1 reverse signaling. While this signaling is beneficial for cancer progression, little is understood about the consequences of PD-L1 reverse signaling in immune cells that express PD-L1 at steady state or in response to infection. Loss of PD-L1 during infection leads to unchecked T-cell proliferation and increased autoimmune T-cell responses. While the T-cell intrinsic role of PD-1 for inhibiting T-cell responses has been well explored, little to no effort has been directed at investigating the consequences of PD-L1 reverse signaling on the DCs interacting with PD-1+ T cells. We recently reported a defect in dendritic cell (DC) trafficking from the skin to the draining lymph node (LN) following immunization or infection in the absence of PD-L1. We demonstrated that a region within the cytoplasmic tail was responsible for the defect in DC trafficking. Here, we review the processes involved in DC trafficking and highlight what we know about PD-L1 expression, PD-L1 post-translational modifications, PD-L1 intracellular interactions, and PD-L1 extracellular interactions.