Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

Daisuke Tokita, Tina L. Sumpter, Giorgio Raimondi, Alan F. Zahorchak, Zhiliang Wang, Atsunori Nakao, George V. Mazariegos, Masanori Abe, Angus W. Thomson

Research output: Contribution to journalArticle

Abstract

Background/Aims: The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), - innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods: Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg). Results: While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4+T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4+CD25+ regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusions: The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity.

Original languageEnglish (US)
Pages (from-to)1008-1018
Number of pages11
JournalJournal of Hepatology
Volume49
Issue number6
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Keywords

  • Dendritic cells
  • Endotoxin
  • Liver
  • Mouse
  • T cells
  • Tolerance
  • Toll-like receptor

ASJC Scopus subject areas

  • Hepatology

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  • Cite this

    Tokita, D., Sumpter, T. L., Raimondi, G., Zahorchak, A. F., Wang, Z., Nakao, A., Mazariegos, G. V., Abe, M., & Thomson, A. W. (2008). Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells. Journal of Hepatology, 49(6), 1008-1018. https://doi.org/10.1016/j.jhep.2008.07.028