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

E. Butti, A. Bergami, A. Recchia, E. Brambilla, U. Del Carro, S. Amadio, A. Cattalini, M. Esposito, A. Stornaiuolo, G. Comi, S. Pluchino, F. Mavilio, G. Martino, R. Furlan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)504-515
Number of pages12
JournalGene Therapy
Volume15
Issue number7
DOIs
Publication statusPublished - Apr 2008

ASJC Scopus subject areas

  • Genetics

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