2026-04-17T13:04:38Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/83962024-12-13T10:46:51Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

Therapeutic Effect of IL-21 Blockage by Gene Therapy in Experimental Autoimmune Encephalomyelitis Edo Salvador, Angel Calvo Barreiro, Laura Eixarch Ahufinger, Herena Bosch Merino, Assumpció Chillon Rodriguez, Miguel Espejo Ruiz, Carmen Teràpia genètica Esclerosi múltiple - Tractament Encefalomielitis - Tractament DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Nervous System Autoimmune Disease, Experimental::Encephalomyelitis, Autoimmune, Experimental Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic Therapy ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes experimentales del sistema nervioso::encefalomielitis autoinmune experimental Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genética Soluble receptor; Multiple sclerosis Receptor soluble; Esclerosis múltiple Receptor soluble; Esclerosi múltiple The pathogenic role of the interleukin 21 (IL-21) in different autoimmune diseases, such as multiple sclerosis (MS), has been extensively studied. However, its pleiotropic nature makes it a cytokine that may exhibit different activity depending on the immunological stage of the disease. In this study, we developed a gene therapy strategy to block the interaction between IL-21 and its receptor (IL-21R) by using adeno-associated vectors (AAV) encoding a new soluble cytokine receptor (sIL21R) protein. We tested this strategy in a murine model of experimental autoimmune encephalomyelitis (EAE), obtaining different clinical effects depending on the time at which the treatment was applied. Although the administration of the treatment during the development of the immune response was counterproductive, the preventive administration of the therapeutic vectors showed a protective effect by reducing the number of animals that developed the disease, as well as an improvement at the histopathological level and a modification of the immunological profile of the animals treated with the AAV8.sIL21R. The beneficial effect of the treatment was also observed when inducing the expression of the therapeutic molecule once the first neurological signs were established in a therapeutic approach with a doxycyline (Dox)-inducible expression system. All these clinical results highlight the pleiotropicity of this cytokine in the different clinical stages and its key role in the EAE immunopathogenesis. Open Access Funding provided by Universitat Autonoma de Barcelona. This project was supported by the Ministerio Ciencia Innovación, retos Sociedad (PI15/0271). A.E was a recipient of a VHIR fellowship. 2023-11-08T13:41:27Z 2023-11-08T13:41:27Z 2023-11-08T13:41:27Z 2022-11-04T08:54:55Z 2022-11-04T08:54:55Z 2022-09 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/8396 Neurotherapeutics;19 https://doi.org/10.1007/s13311-022-01279-8 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Springer Scientia