The role of CD11c+ hepatic dendritic cells in the induction of innate immune responses

Authors

  • S.-A. Shu,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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    • S. A. S and Z. X. L contributed equally to this work.

  • Z.-X. Lian,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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    • S. A. S and Z. X. L contributed equally to this work.

  • Y.-H. Chuang,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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  • G.-X. Yang,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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  • Y. Moritoki,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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  • S. S. Comstock,

    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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  • R.-Q. Zhong,

    1. Department of Laboratory Diagnostics, Changzheng Hospital, Second Military Medical University, Shanghai, China,
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  • A. A. Ansari,

    1. Department of Pathology, Emory University School of Medicine, Atlanta, GA, and
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  • Y.-J. Liu,

    1. Department of Immunology, MD Anderson Cancer Center, Houston, TX, USA
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  • M. E. Gershwin

    Corresponding author
    1. Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA,
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Dr M. Eric Gershwin, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 E. Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
E-mail: megershwin@ucdavis.edu

Summary

The role of the liver in the initiation and maintenance of tolerance is a critical immune function that involves multiple lineages of immune cells. Included within these populations are liver dendritic cells (DCs). Although there has been significant work on the phenotypic and functional roles of splenic and bone marrow dendritic cells, as well as their subsets, comparable studies in liver have often been difficult. To address this issue we have isolated, from C57BL/6 mice, relatively pure populations of DCs and compared phenotype and function to the data from spleen using flow cytometry, cell sorter assisted purification and culture, morphology by cytospin and May–Giemsa staining, cell cycle progression, antigen uptake, cytokine production and allo-activation potential. natural killer (NK)1·1CD11c+ liver DC subsets (conventional DCs, T cell receptor (TcR)βNK1·1CD11c+B220 and plasmacytoid DCs, TcRβNK1·1CD11c+B220+) efficiently endocytose dextran and produce significant levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12 p40 in response to Toll-like receptor (TLR) ligands, with responses higher than splenic DCs. There is also a differential capability of hepatic DCs to respond to innate signals. Indeed, CD11c+ hepatic DCs have a greater capacity to respond to innate stimulation but are less capable of inducing CpG activated-allogeneic T cells. These data suggest that hepatic dendritic cells function as a critical bridge between innate and adaptive immunity and are capable of inducing stronger innate responses with a lower capacity for allo-stimulation than splenic dendritic cells. These properties of liver dendritic cells contribute to their unique role in the induction of tolerance.

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