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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2777-2785.
Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-05-1803.
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IMMUNOBIOLOGY
A transforming growth factor– –induced protein stimulates endocytosis and is up-regulated in immature dendritic cells
Weiping Cao,
Patrick Tan,
Chee How Lee,
Haifeng Zhang, and
Jinhua Lu
From the Department of Microbiology and National University Medical Institute, Yong Loo Lin School of Medicine, National University of Singapore; National Cancer Centre and Genome Institute of Singapore; and Immunology Program, National University of Singapore.
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- –induced protein (ig-h3) was identified as being most prominently up-regulated in imDCs. By polymerase chain reaction (PCR), little ig-h3 mRNA was detected in monocytes and macrophages, but it was abundant in imDCs. On DC activation with LPS, ig-h3 mRNA became diminished, and in tissues, ig-h3 mRNA was abundantly expressed in lymphoid-rich tissues such as the spleen, bone marrow, small intestines, and colon. ig-h3 was expressed in 293T cells and purified as a 70-kDa protein and, by Western blotting, ig-h3 was predominantly detected in the medium of imDCs. We demonstrate that ig-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–ig-h3 antibodies. Therefore, ig-h3 appears to be selectively up-regulated in imDCs to regulate antigen uptake through endocytosis.
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