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.
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.
Choi
Seung-Chul
SC
Laboratory of Cell Biology, Korea Reseach Institute of Bioscience and Biotechnology, Daejeon, Korea.
Kim
Kwang Dong
KD
Kim
Jong-Tae
JT
Kim
Jae Wha
JW
Lee
Hee Gu
HG
Kim
Jin-Man
JM
Jang
Yong-Suk
YS
Yoon
Do-Young
DY
Kim
Keun Il
KI
Yang
Young
Y
Cho
Dae Ho
DH
Lim
Jong-Seok
JS
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
D020410:Activated-Leukocyte Cell Adhesion Molecule; C466228:NDRG2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor