Murine liver plasmacytoid dendritic cells become potent... : Hepatology (original) (raw)

Original Articles

Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion

Kingham, Peter T.1; Chaudhry, Umer I.1; Plitas, George1; Katz, Steven C.1; Raab, Jesse1; DeMatteo, Ronald P.1*

1_Memorial Sloan-Kettering Cancer Center, New York, NY_

*Address reprint requests to: Memorial Sloan-Kettering Cancer Center, Box 203, 1275 York Avenue, New York, NY 10021

Email:[email protected]

Received 3 May 2006; Accepted 11 October 2006

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: NIH; Grant Number: DK068346.

Potential conflict of interest: Nothing to report.

fax: 212-639-4031

Abstract

The liver has unique immunological properties. Although dendritic cells (DCs) are central mediators of immune regulation, little is known about liver DCs. Plasmacytoid DCs (pDCs) are a recently identified subtype of murine liver DC. We sought to define the function of freshly isolated murine liver pDCs. We found that normal liver pDCs were weak in stimulating T cells, yet they possessed a proinflammatory cytokine profile with high tumor necrosis factor-α and low IL-10 secretion. To facilitate the investigation of murine liver pDCs, we expanded them in vivo with fms-like tyrosine kinase 3 ligand (Flt3L). After Toll-like receptor-9 ligation, expanded liver pDCs secreted high levels of IFN-α and were able to stimulate NK cells, NKT cells, and antigen-specific CD8+ T cells in vitro . In addition, Flt3L expansion alone generated pDCs capable of activating antigen-specific CD8+ T cells in vivo .

Conclusion:

Unstimulated liver pDCs exist in a latent state with the potential to become potent activators of the innate and adaptive immune systems through their interactions with other immune effectors. Our findings have implications for understanding the role of the liver in tolerance and immunity.

Abbreviations: CFSE, 5- and 6-carboxy-fluorescein diacetate succinimidyl ester; DC, dendritic cell; FACS, fluorescence-activated cell sorting; Flt3L, fms-like tyrosine kinase 3 ligand; α-GalCer, α-galactosylceramide; NPC, nonparenchymal cell; pDC, plasmacytoid dendritic cell; TCR, T cell receptor.