Suppression of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells.
Neural stem/progenitor cells (NSPCs) have the ability to migrate into the central nervous system (CNS) to replace damaged cells. In inflammatory CNS disease, cytokine transduced neural stem cells may be used as vehicles to specifically reduce inflammation and promote cell replacement. In this study, we used NSPCs overexpressing IL-10, an immunomodulatory cytokine, in an animal model for CNS inflammation and multiple sclerosis (MS). Intravenous injection of IL-10 transduced neural stem/progenitor cells (NSPC(IL-10)) suppressed myelin oligodendrocyte glycoprotein aa 35-55 (MOG35-55)- induced experimental autoimmune encephalomyelitis (EAE) and, following intravenous injection, NSPC(IL-10) migrated to peripheral lymphoid organs and into the CNS. NSPC(IL-10 )suppressed antigen-specific proliferation and proinflammatory cytokine production of lymph node cells obtained from MOG35-55 peptide immunized mice. In this model, IL-10 producing NSPCs act via a peripheral immunosuppressive effect to attenuate EAE.
Center of Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller-Strasse 27, 72076 Tübingen, Germany. felix.bischof@uni-tuebingen.de.
Juliane
J
Klose
Nils Ole
NO
Schmidt
Arthur
A
Melms
Makoto
M
Dohi
Jun-ichi
J
Miyazaki
Felix
F
Bischof
Bernhard
B
Greve
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000276:immunology* / Q000637:transplantation*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods*; D014161:Transduction, Genetic
C556062:IL10 protein, mouse; D016753:Interleukin-10