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IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis.
- Source :
- Gene Therapy; Apr2008, Vol. 15 Issue 7, p504-515, 12p, 2 Color Photographs, 1 Chart, 5 Graphs
- Publication Year :
- 2008
-
Abstract
- Central nervous system (CNS) delivery of anti-inflammatory cytokines, such as interleukin 4 (IL4), holds promise as treatment for multiple sclerosis (MS). We have previously shown that short-term herpes simplex virus type 1-mediated IL4 gene therapy is able to inhibit experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice and non-human primates. Here, we show that a single administration of an IL4-expressing helper-dependent adenoviral vector (HD-Ad) into the cerebrospinal fluid (CSF) circulation of immunocompetent mice allows persistent transduction of neuroepithelial cells and long-term (up to 5 months) CNS transgene expression without toxicity. Mice affected by chronic and relapsing EAE display clinical and neurophysiological recovery from the disease once injected with the IL4-expressing HD-Ad vector. The therapeutic effect is due to the ability of IL4 to increase, in inflamed CNS areas, chemokines (CCL1, CCL17 and CCL22) capable of recruiting regulatory T cells (CD4<superscript>+</superscript>CD69<superscript>−</superscript>CD25<superscript>+</superscript>Foxp3<superscript>+</superscript>) with suppressant functions. CSF delivery of HD-Ad vectors expressing anti-inflammatory molecules might represent a valuable therapeutic option for CNS inflammatory disorders.Gene Therapy (2008) 15, 504–515; doi:10.1038/gt.2008.10; published online 31 January 2008 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09697128
- Volume :
- 15
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 31314674
- Full Text :
- https://doi.org/10.1038/gt.2008.10