IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis
2008; Springer Nature; Volume: 15; Issue: 7 Linguagem: Inglês
10.1038/gt.2008.10
ISSN1476-5462
AutoresErica Butti, Alessandra Bergami, Alessandra Recchia, Elena Brambilla, Ubaldo Del Carro, Stefano Amadio, Alessandro Cattalini, Marianna Esposito, Anna Stornaiuolo, Gıancarlo Comı, Stefano Pluchino, Fulvio Mavilio, Gianvito Martino, Roberto Furlan,
Tópico(s)CAR-T cell therapy research
ResumoCentral 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.
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