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

Dendritic 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-beta-induced protein (betaig-h3) was identified as being most prominently up-regulated in imDCs. By polymerase chain reaction (PCR), little betaig-h3 mRNA was detected in monocytes and macrophages, but it was abundant in imDCs. On DC activation with LPS, betaig-h3 mRNA became diminished, and in tissues, betaig-h3 mRNA was abundantly expressed in lymphoid-rich tissues such as the spleen, bone marrow, small intestines, and colon. betaig-h3 was expressed in 293T cells and purified as a 70-kDa protein and, by Western blotting, betaig-h3 was predominantly detected in the medium of imDCs. We demonstrate that betaig-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-betaig-h3 antibodies. Therefore, betaig-h3 appears to be selectively up-regulated in imDCs to regulate antigen uptake through endocytosis.