PD-L2 (Programmed Death Ligand 2), also known as B7-DC and butyrophilin-like protein, is a transmembrane protein expressed on dendritic cells, subsets of activated CD4+ and CD8+ T cells, and memory B cells that differentiate into plasma cells. At inflammatory sites, PD-L2 is upregulated on synoviocytes, infiltrating macrophages, dendritic cells, and airway epithelial cells. PD-L2, along with B7-H1/PD-L1, binds to T cell PD-1 where it promotes IFN-gamma production and CD40 Ligand upregulation while inhibiting IL-4 production. In addition, PD-L2 binds to RGM-B on macrophages and alveolar epithelial cells, supporting respiratory immune tolerance. In asthma, PD-L2 suppresses IL-5 and IL-13 production, promotes IL-12 production by dendritic cells, and supports allergen-induced airway hyper-responsiveness and mucus production.