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Human astrocyte encapsulation for delivery of cytokines to modulate neuroinflammation

ABSTRACT: Human astrocyte encapsulation for delivery of cytokines to modulate neuroinflammation

PROVIDER: PRJNA1149756 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30296845_1.fastq.gz	Fastqsanger.gz
	SRR30296845_2.fastq.gz	Fastqsanger.gz
	SRR30296846_1.fastq.gz	Fastqsanger.gz
	SRR30296846_2.fastq.gz	Fastqsanger.gz
	SRR30296847_1.fastq.gz	Fastqsanger.gz

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Human astrocyte encapsulation for delivery of cytokines to modulate neuroinflammation

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Project description:The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune-modulation and a delivery system capable of crossing the blood-brain-barrier. The recent identification and characterization of a small population of regulatory T (Treg) cells resident in the brain presents one such potential therapeutic target. Here we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident Treg cells. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Mice with brain-specific IL-2 delivery were protected from traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients.

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