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Fms-Like Tyrosine Kinase 3 Ligand Recruits Plasmacytoid Dendritic Cells to the Brain

James F. Curtin, Gwendalyn D. King, Carlos Barcia, Chunyan Liu, François X. Hubert, Carole Guillonneau, Régis Josien, Ignacio Anegon, Pedro R. Lowenstein and Maria G. Castro
J Immunol March 15, 2006, 176 (6) 3566-3577; DOI: https://doi.org/10.4049/jimmunol.176.6.3566
James F. Curtin
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
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Gwendalyn D. King
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
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Carlos Barcia
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
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Chunyan Liu
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
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François X. Hubert
†Institut National de la Sante et de la Recherche Medicale, Unité 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France; and
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Carole Guillonneau
†Institut National de la Sante et de la Recherche Medicale, Unité 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France; and
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Régis Josien
†Institut National de la Sante et de la Recherche Medicale, Unité 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France; and
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Ignacio Anegon
†Institut National de la Sante et de la Recherche Medicale, Unité 437, and Institut de Transplantation et de Recherche en Transplantation, Nantes, France; and
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Pedro R. Lowenstein
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
‡Department of Molecular and Medical Pharmacology and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90048
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Maria G. Castro
*Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048;
‡Department of Molecular and Medical Pharmacology and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90048
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Abstract

The lack of professional afferent APCs in naive brain parenchyma contributes to the systemic immune ignorance to Ags localized exclusively within the brain. Dendritic cells (DCs) appear within the brain as a consequence of inflammation, but no molecular mechanisms accounting for this influx have been described. In this study we demonstrate that Fms-like tyrosine kinase 3 ligand (Flt3L) recruits plasmacytoid DCs (pDCs; >50-fold; p < 0.001) to the brain parenchyma. These pDCs expressed IFN-α, the hallmark cytokine produced by pDCs, indicating recruitment and activation in situ of bona fide pDCs within the brain parenchyma. Flt3L did not increase the numbers of conventional DCs, macrophages, or B, T, NK, NKT, or microglial cells within the brain. Our data demonstrate that Flt3L reconstitutes a crucial afferent component of the immune response, namely, professional APCs within the brain parenchyma, and this could counteract the intrinsic systemic immune ignorance to Ags localized exclusively within the brain.

  • Received November 11, 2005.
  • Accepted January 10, 2006.
  • Copyright © 2006 by The American Association of Immunologists
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The Journal of Immunology: 176 (6)
The Journal of Immunology
Vol. 176, Issue 6
15 Mar 2006
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Fms-Like Tyrosine Kinase 3 Ligand Recruits Plasmacytoid Dendritic Cells to the Brain
James F. Curtin, Gwendalyn D. King, Carlos Barcia, Chunyan Liu, François X. Hubert, Carole Guillonneau, Régis Josien, Ignacio Anegon, Pedro R. Lowenstein, Maria G. Castro
The Journal of Immunology March 15, 2006, 176 (6) 3566-3577; DOI: 10.4049/jimmunol.176.6.3566

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Fms-Like Tyrosine Kinase 3 Ligand Recruits Plasmacytoid Dendritic Cells to the Brain
James F. Curtin, Gwendalyn D. King, Carlos Barcia, Chunyan Liu, François X. Hubert, Carole Guillonneau, Régis Josien, Ignacio Anegon, Pedro R. Lowenstein, Maria G. Castro
The Journal of Immunology March 15, 2006, 176 (6) 3566-3577; DOI: 10.4049/jimmunol.176.6.3566
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