PMID- 24706756 OWN - NLM STAT- MEDLINE DCOM- 20141028 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 21 DP - 2014 May 23 TI - Homeobox transcription factor VentX regulates differentiation and maturation of human dendritic cells. PG - 14633-43 LID - 10.1074/jbc.M113.509158 [doi] AB - 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. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Wu, Xiaoming AU - Wu X AD - From the Departments of Medicine, Gastroenterology Division and. FAU - Gao, Hong AU - Gao H AD - the Department of Medicine, Tufts Medical Center, Boston, Massachusetts 02111. FAU - Bleday, Ronald AU - Bleday R AD - Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115 and. FAU - Zhu, Zhenglun AU - Zhu Z AD - From the Departments of Medicine, Gastroenterology Division and zzhu@partners.org. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140404 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Glucocorticoids) RN - 0 (Homeodomain Proteins) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (VENTX protein, human) RN - 9PHQ9Y1OLM (Prednisolone) SB - IM MH - Adult MH - Blotting, Western MH - Cell Differentiation/drug effects/*genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cells, Cultured MH - Dendritic Cells/drug effects/*metabolism MH - Gene Expression/drug effects MH - Gene Knockdown Techniques MH - Glucocorticoids/pharmacology MH - Homeodomain Proteins/*genetics/metabolism MH - Humans MH - Inflammatory Bowel Diseases/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Intestinal Mucosa/metabolism/pathology MH - Lipopolysaccharides/pharmacology MH - Monocytes/*metabolism MH - Prednisolone/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC4031519 OTO - NOTNLM OT - Dendritic Cells OT - Development OT - Differentiation OT - Gene Regulation OT - Monocytes EDAT- 2014/04/08 06:00 MHDA- 2014/10/29 06:00 PMCR- 2015/05/23 CRDT- 2014/04/08 06:00 PHST- 2014/04/08 06:00 [entrez] PHST- 2014/04/08 06:00 [pubmed] PHST- 2014/10/29 06:00 [medline] PHST- 2015/05/23 00:00 [pmc-release] AID - S0021-9258(20)38667-1 [pii] AID - M113.509158 [pii] AID - 10.1074/jbc.M113.509158 [doi] PST - ppublish SO - J Biol Chem. 2014 May 23;289(21):14633-43. doi: 10.1074/jbc.M113.509158. Epub 2014 Apr 4.