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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / metabolism
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Animals
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Biological Factors / pharmacology
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Cell Differentiation
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Colony-Forming Units Assay
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Culture Media, Conditioned / pharmacology
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Cytokines / pharmacology
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Dendritic Cells / cytology*
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Dendritic Cells / metabolism
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Endothelial Growth Factors / pharmacology
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Female
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Gene Expression Regulation
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / metabolism
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Histones / deficiency
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Histones / genetics
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Histones / physiology*
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Immunologic Surveillance
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Lymphocyte Activation
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Lymphocytes / cytology
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Lymphocytes / metabolism
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Lymphokines / pharmacology
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Membrane Proteins / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Models, Immunological
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Myeloid Cells / cytology
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Myeloid Cells / metabolism
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NF-kappa B / metabolism
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Neoplasms, Experimental / immunology*
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Neoplasms, Experimental / metabolism
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Neoplasms, Experimental / pathology
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Phagocytosis
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Recombinant Proteins / pharmacology
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Tumor Cells, Cultured / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / pharmacology
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Vaccination
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Biological Factors
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Culture Media, Conditioned
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Cytokines
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Endothelial Growth Factors
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Histones
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Lymphokines
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Membrane Proteins
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NF-kappa B
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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flt3 ligand protein