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+CD69-CD25+Foxp3+) with suppressant functions. CSF delivery of HD-Ad vectors expressing anti-inflammatory molecules might represent a valuable therapeutic option for CNS inflammatory disorders.

IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis / Butti, E; Bergami, A; Recchia, Alessandra; Brambilla, E; Del Carro, U; Amadio, S; Cattalini, A; Esposito, M; Stornaiuolo, A; Comi, G; Pluchino, S; Mavilio, Fulvio; Martino, G; Furlan, R.. - In: GENE THERAPY. - ISSN 0969-7128. - STAMPA. - 15:(2008), pp. 504-515. [10.1038/gt.2008.10]

IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis

RECCHIA, Alessandra;MAVILIO, Fulvio;
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+CD69-CD25+Foxp3+) with suppressant functions. CSF delivery of HD-Ad vectors expressing anti-inflammatory molecules might represent a valuable therapeutic option for CNS inflammatory disorders.
2008
15
504
515
IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis / Butti, E; Bergami, A; Recchia, Alessandra; Brambilla, E; Del Carro, U; Amadio, S; Cattalini, A; Esposito, M; Stornaiuolo, A; Comi, G; Pluchino, S; Mavilio, Fulvio; Martino, G; Furlan, R.. - In: GENE THERAPY. - ISSN 0969-7128. - STAMPA. - 15:(2008), pp. 504-515. [10.1038/gt.2008.10]
Butti, E; Bergami, A; Recchia, Alessandra; Brambilla, E; Del Carro, U; Amadio, S; Cattalini, A; Esposito, M; Stornaiuolo, A; Comi, G; Pluchino, S; Mav...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/613136
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