Ligation of the BT3 molecules, members of the B7 family, enhance the proinflammatory responses of human monocytes and monocyte-derived dendritic cells

Abstract BT3 is a new family of immunoreceptors belonging to the extended B7 family. BT3 molecules are expressed on the surface of resting and activated monocytes and monocyte-derived dendritic cells (iDC). We show that BT3 cross-linking, in the absence of other survival factors, provides a survival signal for monocytes and iDC and induces up-regulation of costimulatory molecules, such as CD80 and CD86, and HLA-DR. We further analyzed the effects of BT3 cross-linking on various proinflammatory responses on monocytes and iDC. The results obtained showed that BT3 engagement is able to modulate the production of IL8/CXCL8, IL-1β and IL-12/p70. Moreover, we demonstrated a synergistic effect between BT3 and Toll-like receptors ligands on both monocytes and iDC in up-regulating the production of proinflammatory cytokines. Thus, BT3 could be involved in the regulation of the balance between immune activation and suppression. A better understanding of its physiological role of these families of receptors awaits the precise identification of the nature, origin, expression, and distribution of their ligands.