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

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