Autor(es):
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
Data: 2022
Identificador Persistente: https://hdl.handle.net/10216/142881
Origem: Repositório Aberto da Universidade do Porto
Descrição
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.
