title: H1(0) histone and differentiation of dendritic cells. A molecular target for tumor-derived factors.
abstract: Dendritic cells (DC) play a central role in antitumor immune responses. Abnormal differentiation of DC and their inability to stimulate T cells are important factors in tumor escape from immune-system control. However, the mechanisms of this process remain elusive. Here, we have described one possible molecular mechanism that involves replacement linker histone H1 (0). A close association between expression of H1(0) and DC differentiation in vitro has been found. DC production in H1(0) -deficient mice was decreased significantly, whereas generation and function of macrophages, granulocytes, and lymphocytes appear to be normal. However, these mice had a significantly reduced response to vaccination with antigens. Tumor-derived factors considerably reduced H1(0) expression in hematopoietic progenitor cells. We have demonstrated that transcription factor NF-kappaB is involved actively in regulation of H1(0). Thus, H1(0) histone may be an important factor in normal DC differentiation. Tumor-derived factors may inhibit DC differentiation by affecting H1(0) expression.
authors.affiliation: H. Lee Moffitt Cancer Center, University of South Florida, Tampa 33612, USA. dgabril@moffitt.usf.edu
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
authors.forename: Pingyan
authors.initials: P
authors.lastname: Cheng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Fan
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Nikitina
authors.forename: Allen
authors.initials: A
authors.lastname: Sirotkin
authors.forename: Michael
authors.initials: M
authors.lastname: Shurin
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Sorena
authors.initials: S
authors.lastname: Nadaf
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Skoultchi
mesh_terms: D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007157:Immunologic Surveillance; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014611:Vaccination; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D001685:Biological Factors; D017077:Culture Media, Conditioned; D016207:Cytokines; D016228:Endothelial Growth Factors; D006657:Histones; D008222:Lymphokines; D008565:Membrane Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C084881:flt3 ligand protein