H1° histone and differentiation of dendritic cells. A molecular target for tumor-derived factors

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

Research output: Contribution to journalArticle

41 Scopus citations

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°. A close association between expression of H1° and DC differentiation in vitro has been found. DC production in H1°-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° expression in hematopoietic progenitor cells. We have demonstrated that transcription factor NF-κB is involved actively in regulation of h1°. Thus, H1° histone may be an important factor in normal DC differentiation. Tumor-derived factors may inhibit DC differentiation by affecting H1° expression.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalJournal of Leukocyte Biology
Volume72
Issue number2
Publication statusPublished - Aug 1 2002

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Keywords

  • Cellular differentiation
  • Monocytes/macrophages
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Gabrilovich, D. I., Cheng, P., Fan, Y., Yu, B., Nikitina, E., Sirotkin, A., ... Skoultchi, A. I. (2002). H1° histone and differentiation of dendritic cells. A molecular target for tumor-derived factors. Journal of Leukocyte Biology, 72(2), 285-296.