|
|
Fms-Like Tyrosine Kinase 3 Ligand
Recruits Plasmacytoid Dendritic Cells to the Brain
James F. Curtin1,
Gwendalyn D. King1, Carlos
Barcia1, Chunyan Liu1,
François X. Hubert2, Carole
Guillonneau, Régis
Josien, Ignacio Anegon,
Pedro R. Lowenstein1,3 and Maria
G. Castro1,3
1Gene Therapeutics
Research Institute, Cedars Sinai Medical Center, Los Angeles, CA
90048; 2Institut National de la Sante et de la
Recherche Medicale, Unité 437, and Institut de Transplantation et de
Recherche en Transplantation, Nantes, France; and 3Department
of Molecular and Medical Pharmacology and Department of Medicine,
David Geffen School of Medicine, University of California, Los
Angeles, CA 90048.
|
|
|
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.
|
