Homeobox transcription factor VentX regulates differentiation and maturation of human dendritic cells.
Dendritic cells (DCs) are specialized antigen presentation cells that play critical roles in the initiation and regulation of immune responses. The molecular determinants of DC differentiation and maturation are target of extensive investigation. VentX is a human homeobox transcriptional factor that regulates proliferation and differentiation of hematopoietic cells. In the current study, we report that ablation of VentX expression in monocytes significantly impaired their differentiation into DCs. Conversely, overexpression of VentX in monocytic THP1 cells accelerated their differentiation toward DCs. We showed that VentX regulates DC differentiation, in part, through modulating IL6 expression. Clinically, we found that VentX expression was elevated in intestinal lamina propria DCs (LPDCs) of inflamed mucosa from inflammatory bowel disease patients. Knockdown experiments suggested that VentX is essential for the maturation of LPDCs. In addition, corticosteroid treatment markedly decreased VentX expression in LPDCs and enforced expression of VentX counteracted the effects of corticosteroid on DCs maturation. Our data suggest that VentX is a critical transcriptional regulator of DC differentiation and maturation, and a potential target of immune regulation and therapy.
From the Departments of Medicine, Gastroenterology Division and.
Xiaoming
X
Wu
the Department of Medicine, Tufts Medical Center, Boston, Massachusetts 02111.
Hong
H
Gao
Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115 and.
Ronald
R
Bleday
From the Departments of Medicine, Gastroenterology Division and zzhu@partners.org.
Zhenglun
Z
Zhu
D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D018398:Homeodomain Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; C408346:VENTX protein, human; D011239:Prednisolone
Dendritic Cells; Development; Differentiation; Gene Regulation; Monocytes