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: Dmitry I Gabrilovich, Pingyan Cheng, Yuhong Fan, Bin Yu, Ekaterina Nikitina, Allen Sirotkin, Michael Shurin, Tsunehiro Oyama, Yasushi Adachi, Sorena Nadaf, David P Carbone, Arthur I Skoultchi
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 72 Issue 2 Pg. 285-96 (Aug 2002) ISSN: 0741-5400 [Print] United States
• PMID: 12149419 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biological Factors
• Culture Media, Conditioned
• Cytokines
• Endothelial Growth Factors
• Histones
• Lymphokines
• Membrane Proteins
• NF-kappa B
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• flt3 ligand protein

Topics

• 3T3 Cells (metabolism)
• Animals
• Biological Factors (pharmacology)
• Cell Differentiation
• Colony-Forming Units Assay
• Culture Media, Conditioned (pharmacology)
• Cytokines (pharmacology)
• Dendritic Cells (cytology, metabolism)
• Endothelial Growth Factors (pharmacology)
• Female
• Gene Expression Regulation
• Hematopoietic Stem Cells (cytology, metabolism)
• Histones (deficiency, genetics, physiology)
• Immunologic Surveillance
• Lymphocyte Activation
• Lymphocytes (cytology, metabolism)
• Lymphokines (pharmacology)
• Membrane Proteins (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Immunological
• Myeloid Cells (cytology, metabolism)
• NF-kappa B (metabolism)
• Neoplasms, Experimental (immunology, metabolism, pathology)
• Phagocytosis
• Recombinant Proteins (pharmacology)
• Tumor Cells, Cultured (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis, pharmacology)
• Vaccination
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors