IMMUNOBIOLOGY Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-

Dendritic cells (DCs) are the most potent antigen-presenting cells for naive T cells. In this study, scavenger receptor class A type I and type II (SR-A) were shown to be expressed by peripheral blood DCs (PBDCs) and monocyte-derived DCs (MDDCs). In addition, the binding of anti–SR-A antibody to these cells was lower in the presence of fucoidan, an SR-A agonist. Treatment of these DCs with fucoidan or anti–SR-A antibodymarkedly increasedthesurfaceexpression of costimulatory molecules CD83 and major histocompatibility complex class II on the CD11chighCD123low myeloid subset of PBDCs. Furthermore, fucoidan-treated PBDCs produced tumor necrosis factor(TNF) but not IL-12p70. In addition, fucoidan-induced maturation was eliminated by pretreatment with TNF– neutralizing antibody. Finally, interferonsecretion and T-cell proliferation were enhanced by coculture of T cells with fucoidan-matured PBDCs. Specific inhibitors of p38 MAPK and glycogen synthase kinase 3 suppressed TNFproduction and maturation of fucoidantreated PBDCs. Moreover, MDDCs lacking SR-A failed to up-regulate CD83 expression, TNFproduction, and phosphorylation of p38 MAPK and glycogen synthase kinase 3in the presence of fucoidan. Taken together, these results suggest that ligation of SR-A leads to induction of TNF, which subsequently induces PBDC maturation, thereby leading to enhanced T-cell stimulatory capacity. (Blood. 2009;113:5839-5847)