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

39 Citations (Scopus)

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
Pages (from-to)1008-1018
Number of pages11
JournalJournal of Hepatology
Volume49
Issue number6
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

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Regulatory T-Lymphocytes
Dendritic Cells
Liver
T-Lymphocytes
Interleukin-10
Spleen
Cell Proliferation
Ligands
Vascular Endothelial Growth Factor Receptor-1
Th2 Cells
Adaptive Immunity
Inbred C57BL Mouse
Biological Assay
Lipopolysaccharides
Cell Differentiation
Apoptosis
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Hepatology

Cite this

Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells. / Tokita, Daisuke; Sumpter, Tina L.; Raimondi, Giorgio; Zahorchak, Alan F.; Wang, Zhiliang; Nakao, Atsunori; Mazariegos, George V.; Abe, Masanori; Thomson, Angus W.

In: Journal of Hepatology, Vol. 49, No. 6, 12.2008, p. 1008-1018.

Research output: Contribution to journalArticle

Tokita, D, Sumpter, TL, Raimondi, G, Zahorchak, AF, Wang, Z, Nakao, A, Mazariegos, GV, Abe, M & Thomson, AW 2008, 'Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells', Journal of Hepatology, vol. 49, no. 6, pp. 1008-1018. https://doi.org/10.1016/j.jhep.2008.07.028
Tokita, Daisuke ; Sumpter, Tina L. ; Raimondi, Giorgio ; Zahorchak, Alan F. ; Wang, Zhiliang ; Nakao, Atsunori ; Mazariegos, George V. ; Abe, Masanori ; Thomson, Angus W. / Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells. In: Journal of Hepatology. 2008 ; Vol. 49, No. 6. pp. 1008-1018.
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AU - Zahorchak, Alan F.

AU - Wang, Zhiliang

AU - Nakao, Atsunori

AU - Mazariegos, George V.

AU - Abe, Masanori

AU - Thomson, Angus W.

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AB - 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.

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