Journal
JOURNAL OF HEPATOLOGY
Volume 49, Issue 6, Pages 1008-1018Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2008.07.028
Keywords
Dendritic cells; Liver; T cells; Mouse; Endotoxin; Toll-like receptor; Tolerance
Categories
Funding
- National Institutes Of Health (NIH) [R01 DK 49745, R01 AI60994]
- Uehara Foundation
- The Hillman Pediatric Transplant Center, Children's Hospital of Pittsburgh
- American Liver Foundation
- American Society of Transplantation Basic Science Fellowship
- [NIH T32 CA82084]
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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. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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