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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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Submitted May 5, 2005
Accepted October 29, 2005

A transforming growth factor {beta}-induced protein stimulates endocytosis and is up-regulated at the immature state of dendritic cells

Weiping Cao, Patrick Tan, Chee H Lee, Haifeng Zhang, and Jinhua Lu*

Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Medical Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
National Cancer Centre, Singapore, Singapore; Genome Institute of Singapore, Singapore, Singapore
National Cancer Centre, Singapore, Singapore
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Medical Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Immunology Program, National University of Singapore, Singapore, Singapore

* Corresponding author; email: miclujh{at}nus.edu.sg.

Dendritic cells (DCs) exhibit distinct functional properties at immature and mature states. To identify genes that are 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 ({beta}ig-h3) was identified as being most prominently up-regulated in imDCs. By PCR, little {beta}ig-h3 mRNA was detected in monocytes and macrophages but it was abundant in imDCs. Upon DC activation with LPS, {beta}ig-h3 mRNA became diminished, and in tissues, {beta}ig-h3 mRNA was abundantly expressed in lymphoid-rich tissues such as the spleen, bone marrow, small intestines and colons. {beta}ig-h3 was expressed in 293T cells and purified as a 70 kDa protein and, by Western blotting, {beta}ig-h3 was predominantly detected in the medium of imDCs. We demonstrate that {beta}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-{beta}ig-h3 antibodies. Therefore, {beta}ig-h3 appears to be selectively up-regulated in imDCs to regulate antigen uptake through endocytosis.


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