Therapeutic Effect of IL-21 Blockage by Gene Therapy in Experimental Autoimmune Encephalomyelitis
Edo Salvador, Ángel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Calvo-Barreiro, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Eixarch, Herena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bosch i Merino, Assumpció (Universitat Autònoma de Barcelona. Institut de Neurociències)
Chillón Rodríguez, Miguel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Espejo, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Data:	2022
Resum:	The pathogenic role of the interleukin 21 (IL-21) in diferent autoimmune diseases, such as multiple sclerosis (MS), has been extensively studied. However, its pleiotropic nature makes it a cytokine that may exhibit diferent 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 diferent clinical efects 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 efect by reducing the number of animals that developed the disease, as well as an improvement at the histopathological level and a modifcation of the immunological profle of the animals treated with the AAV8. sIL21R. The beneficial efect of the treatment was also observed when inducing the expression of the therapeutic molecule once the frst 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 diferent clinical stages and its key role in the EAE immunopathogenesis.
Ajuts:	Ministerio de Ciencia e Innovación PI15/0271
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	IL-21 ; Soluble receptor ; EAE ; Multiple sclerosis ; AAV
Publicat a:	Neurotherapeutics, Vol. 19 (july 2022) , p. 1617-1633, ISSN 1878-7479

DOI: 10.1007/s13311-022-01279-8
PMID: 35902536

17 p, 1.8 MB

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