A transforming growth factor–β–induced protein stimulates endocytosis and is up-regulated in immature dendritic cells

Abstract

AbstractDendritic cells (DCs) exhibit distinct functional properties at immature and mature states. To identify genes preferentially regulated in monocyte-derived immature DCs (imDCs), 13 000-element microarrays were hybridized with RNA isolated from imDCs, mature DCs (mDCs), monocytes, and macrophages and a TGF-β–induced protein (βig-h3) was identified as being most prominently up-regulated in imDCs. By polymerase chain reaction (PCR), little βig-h3 mRNA was detected in monocytes and macrophages, but it was abundant in imDCs. On DC activation with LPS, βig-h3 mRNA became diminished, and in tissues, βig-h3 mRNA was abundantly expressed in lymphoid-rich tissues such as the spleen, bone marrow, small intestines, and colon. βig-h3 was expressed in 293T cells and purified as a 70-kDa protein and, by Western blotting, βig-h3 was predominantly detected in the medium of imDCs. We demonstrate that βig-h3 binds to macrophages and imDCs but not to mDCs and activates the Rac GTPase in macrophages, stimulating macrophage membrane ruffling and enhancing macrophage endocytosis. imDC endocytosis was also inhibited by purified anti–βig-h3 antibodies. Therefore, βig-h3 appears to be selectively up-regulated in imDCs to regulate antigen uptake through endocytosis.