Programmed Death Ligand 2 (PD-L2); also known as B7-DC and butyrophilin-like protein; is a member of the B7 family of proteins that provide signals for regulating T-cell activation and tolerance .PD-L2 is expressed on dendritic cells; subsets of activated CD4+ and CD8+ T cells; and memory B cells that differentiate into plasma cells. At inflammatory sites such as rheumatoid arthritis; allergen exposure; and virus infection; PD-L2 is up-regulated 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 up-regulation 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.