PMID- 16517725 OWN - NLM STAT- MEDLINE DCOM- 20060424 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 176 IP - 6 DP - 2006 Mar 15 TI - Fms-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain. PG - 3566-77 AB - 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-alpha, 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. FAU - Curtin, James F AU - Curtin JF AD - Gene Therapeutics Research Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. FAU - King, Gwendalyn D AU - King GD FAU - Barcia, Carlos AU - Barcia C FAU - Liu, Chunyan AU - Liu C FAU - Hubert, Francois X AU - Hubert FX FAU - Guillonneau, Carole AU - Guillonneau C FAU - Josien, Regis AU - Josien R FAU - Anegon, Ignacio AU - Anegon I FAU - Lowenstein, Pedro R AU - Lowenstein PR FAU - Castro, Maria G AU - Castro MG LA - eng GR - 1R03 TW 006273-01/TW/FIC NIH HHS/United States GR - R21 NS 047298-01/NS/NINDS NIH HHS/United States GR - R21 NS047298/NS/NINDS NIH HHS/United States GR - R01 NS044556/NS/NINDS NIH HHS/United States GR - U54 NS045309/NS/NINDS NIH HHS/United States GR - 1R01 NS 42893-01/NS/NINDS NIH HHS/United States GR - U54 NS 045309-01/NS/NINDS NIH HHS/United States GR - R01 NS042893/NS/NINDS NIH HHS/United States GR - R03 TW006273/TW/FIC NIH HHS/United States GR - 1R01 NS 44556-01/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Biomarkers) RN - 0 (Interferon-alpha) RN - 0 (Ligands) RN - 0 (TLR7 protein, rat) RN - 0 (Toll-Like Receptor 7) RN - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3) SB - IM MH - Animals MH - B-Lymphocytes/metabolism MH - Biomarkers MH - Brain/*cytology/*metabolism MH - Cell Movement MH - Cell Separation MH - Dendritic Cells/*cytology/*metabolism MH - Gene Expression Regulation/genetics MH - Humans MH - Interferon-alpha/genetics/metabolism MH - Ligands MH - Male MH - Organ Specificity MH - Rats MH - Toll-Like Receptor 7/genetics/metabolism MH - fms-Like Tyrosine Kinase 3/genetics/*metabolism PMC - PMC1592227 MID - NIHMS11836 COIS- Disclosures The authors have no financial conflict of interest. EDAT- 2006/03/07 09:00 MHDA- 2006/04/25 09:00 PMCR- 2008/02/01 CRDT- 2006/03/07 09:00 PHST- 2006/03/07 09:00 [pubmed] PHST- 2006/04/25 09:00 [medline] PHST- 2006/03/07 09:00 [entrez] PHST- 2008/02/01 00:00 [pmc-release] AID - 176/6/3566 [pii] AID - 10.4049/jimmunol.176.6.3566 [doi] PST - ppublish SO - J Immunol. 2006 Mar 15;176(6):3566-77. doi: 10.4049/jimmunol.176.6.3566.