Autoantigen-pulsed dendritic cells constitute a beneficial cytokine and growth factor network in ameliorating experimental allergic encephalomyelitis.
Injection of myelin basic protein (MBP)-pulsed dendritic cells (DC) into healthy rats, as we reported before and observed in this study, did not induce clinical experimental allergic encephalomyelitis (EAE), but effectively protected the rats from subsequent EAE induction. The mechanisms by which MBP-pulsed DC mediate immune protection are not completely understood. In the present study, we mainly explored the dynamic change of cytokine and growth factor mRNA expression in spinal cords after subcutaneous injection of MBP-pulsed and unpulsed DC. The expression of interleukin (IL)-1, interferon-gamma and tumour necrosis factor-alpha as well as programmed death ligand (PDL)-1, PDL-2, signal transducer and activator of transcription (STAT)4, STAT6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-2 was increased on day 0 postimmunization (p.i.). The increase of IL-12 expression was observed on day 7 p.i., while the increase of IL-10 expression mainly occurred on day 14 p.i. Except downregulation of insulin-like growth factor-1, the expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-B/C as well as nerve growth factor receptor (NGF-R), FGF receptor, PDGF-R-alpha and beta was elevated on day 0 p.i., while the increase of TIMP and NGF was observed on days 0 and 7 p.i. There were no significant differences on MMP-2, spinal cord-derived growth factor and PDGF-A mRNA expression. In line with the suppression of EAE induced by MBP-pulsed DC, the dynamic change of cytokines and growth factors in spinal cords should constitute a beneficial microenvironment against EAE.
Liu
Xuan
X
Division of Neuroimmunology, Neurotec Department, Karolinska Institute, 14183 Huddinge, Stockholm, Sweden.
Ciumas
Carolina
C
Huang
Yu-Min
YM
Steffensen
Knut R
KR
Lian
Hong
H
Link
Hans
H
Xiao
Bao-Guo
BG
D000818:Animals; D001324:Autoantigens / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew
D001324:Autoantigens; D016207:Cytokines; D017931:DNA Primers; D006133:Growth Substances