Fms-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain

被引：69
作者：
Curtin, James F.
King, Gwendalyn D.
Barcia, Carlos
Liu, Chunyan
Hubert, Franiqois X.
Guillonneau, Carole
Josien, Regis
Anegon, Ignacio
Lowenstein, Pedro R.
Castro, Maria G.
机构：
[1] Cedars Sinai Med Ctr, Gene Therapeut Res Inst, Los Angeles, CA 90048 USA
[2] Inst Natl Sante & Rech Med, Unite 437, Nantes, France
[3] Inst Transplantat & Rech Transplantat, Nantes, France
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90048 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA
来源：
JOURNAL OF IMMUNOLOGY | 2006年 / 176卷 / 06期
关键词：
D O I：
10.4049/jimmunol.176.6.3566
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：3566 / 3577
页数：12
相关论文
共 47 条
[1]   Inflammatory and anti-glioma effects of an adenovirus expressing human-soluble Fms-like tyrosine kinase 3 ligand (hsFIt3L): Treatment with hsFIt3L inhibits intracranial glioma progression [J].
Ali, S ;
Curtin, JF ;
Zirger, JM ;
Xiong, WD ;
King, GD ;
Barcia, C ;
Liu, CY ;
Puntel, M ;
Goverdhana, S ;
Lowenstein, PR ;
Castro, MG .
MOLECULAR THERAPY, 2004, 10 (06) :1071-1084
[2]   Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model [J].
Ali, S ;
King, GD ;
Curtin, JF ;
Candolfi, M ;
Xiong, WD ;
Liu, CY ;
Puntel, M ;
Cheng, Q ;
Prieto, J ;
Ribas, A ;
Kupiec-Weglinski, J ;
van Rooijen, N ;
Lassmann, H ;
Lowenstein, PR ;
Castro, MG .
CANCER RESEARCH, 2005, 65 (16) :7194-7204
[3]   Production of type I interferons: plasmacytoid dendritic cells and beyond [J].
Asselin-Paturel, C ;
Trinchieri, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (04) :461-465
[4]   Mouse type IIFN-producing cells are immature APCs with plasmacytoid morphology [J].
Asselin-Paturel, C ;
Boonstra, A ;
Dalod, M ;
Durand, I ;
Yessaad, N ;
Dezutter-Dambuyant, C ;
Vicari, A ;
O'Garra, A ;
Biron, C ;
Brière, F ;
Trinchieri, G .
NATURE IMMUNOLOGY, 2001, 2 (12) :1144-1150
[5]   The FLT3 tyrosine kinase receptor inhibits neural stem/progenitor cell proliferation and collaborates with NGF to promote neuronal survival [J].
Brazel, CY ;
Ducceschi, MH ;
Pytowski, B ;
Levison, SW .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2001, 18 (04) :381-393
[6]   Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells [J].
Carson, MJ ;
Reilly, CR ;
Sutcliffe, JG ;
Lo, D .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (02) :481-494
[7]   Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent THI polarization [J].
Cella, M ;
Facchetti, F ;
Lanzavecchia, A ;
Colonna, M .
NATURE IMMUNOLOGY, 2000, 1 (04) :305-310
[8]   Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon [J].
Cella, M ;
Jarrossay, D ;
Facchetti, F ;
Alebardi, O ;
Nakajima, H ;
Lanzavecchia, A ;
Colonna, M .
NATURE MEDICINE, 1999, 5 (08) :919-923
[9]   CELLULAR-FORMS AND FUNCTIONS OF BRAIN MICROGLIA [J].
DAVIS, EJ ;
FOSTER, TD ;
THOMAS, WE .
BRAIN RESEARCH BULLETIN, 1994, 34 (01) :73-78
[10]   Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: Implications for clinical trials [J].
Dewey, RA ;
Morrissey, G ;
Cowsill, CM ;
Stone, D ;
Bolognani, F ;
Dodd, NJF ;
Southgate, TD ;
Klatzmann, D ;
Lassmann, H ;
Castro, MG ;
Lowenstein, PR .
NATURE MEDICINE, 1999, 5 (11) :1256-1263
12345