Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/142881
Author(s): | Yshii, L Pasciuto, E Bielefeld, P Mascali, L Lemaitre, P Marino, M Dooley, J Kouser, L Verschoren, S Lagou, V Kemps, H Gervois, P Boer, A Burton, OT Wahis, J Verhaert, J Tareen, SHK Roca, CP Singh, K Whyte, CE Kerstens, A Callaerts-Vegh, Z Poovathingal, S Prezzemolo, T Wierda, K Dashwood, A Xie, J Wonterghem, E Creemers, E Aloulou, M Gsell, W Abiega, O Munck, S Vandenbroucke, RE Bronckaers, A Lemmens, R Strooper, B Den Bosch, L Himmelreich, U Fitzsimons, CP Holt, MG Liston, A |
Title: | Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation |
Publisher: | Nature Publishing Group |
Issue Date: | 2022 |
Abstract: | 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 in 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. |
URI: | https://hdl.handle.net/10216/142881 |
Series: | Nature immunology, vol.23(6), p. 878-891 |
Related Information: | info:eu-repo/grantAgreement/EC/H2020/951923/EU |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
License: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | I3S - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
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10.1038-s41590-022-01208-z.pdf | 13.67 MB | Adobe PDF | View/Open | |
Sup. Inf. - 10.1038-s41590-022-01208-z.pdf | 10.53 MB | Adobe PDF | View/Open |
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