Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0507300 on October 2, 2007

Published online before print October 2, 2007
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(Journal of Leukocyte Biology. 2008;83:89-98.)
© 2008 by Society for Leukocyte Biology

Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity

Seung-Chul Choi*,{dagger}, Kwang Dong Kim*, Jong-Tae Kim*, Jae Wha Kim*, Hee Gu Lee*, Jin-Man Kim{ddagger}, Yong-Suk Jang{dagger}, Do-Young Yoon§, Keun Il Kim||, Young Yang||, Dae Ho Cho|| and Jong-Seok Lim||,1

* Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea;
{ddagger} Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Korea;
{dagger} Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju, Korea;
§ Department of Molecular Biotechnology, Konkuk University, Seoul, Korea; and
|| Department of Biological Sciences and the Research Center for Women’s Diseases, Sookmyung Women’s University, Seoul, Korea

1 Correspondence: Department of Biological Sciences and the Research Center for Women’s Diseases, Sookmyung Women’s University, Chungpa-Dong, Yongsan-Gu, Seoul 140-742, Korea. E-mail: jslim{at}sookmyung.ac.kr

We reported previously that N-myc downstream-regulated gene 2 (NDRG2), a member of a new family of differentiation-related genes, is expressed specifically in dendritic cells (DC) differentiated from monocytes, CD34+ progenitor cells, and the myelomonocytic leukemic cell line. In this study, we demonstrate that NDRG2 protein expression is detected, not only in in vitro-differentiated DC but also in primary DC from lymph nodes, thymus, and skin when anti-NDRG2 antibodies are used. As predicted from previous studies investigating the mRNA expression pattern of several types of cell lines, progenitor cells, and DC, NDRG2 protein was expressed strongly in DC. Its expression was detected at significant levels after differentiation from progenitor cells. RNA interference of NDRG2 demonstrated that activated leukocyte cell adhesion molecule (ALCAM) expression is down-regulated specifically in DC differentiated from NDRG2 small interfering RNA (siRNA)-transfected monocytes. This was consistent with our observation that U937 cells transfected with NDRG2 became resistant to the GM-CSF/IL-4-induced ALCAM reduction. Furthermore, DC, which had differentiated from NDRG2 siRNA-transfected monocytes, showed a reduced ability to induce T cell proliferation. Taken together, our results indicate that NDRG2 is able to preserve ALCAM expression during DC differentiation from monocytes under cytokine culture conditions and that its expression helps DC maintain costimulatory signals necessary for T cell stimulation.

Key Words: dendritic cells (DC) • siRNA






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