Detalle Publicación


Treatment of Experimental Autoimmune Encephalomyelitis by Sustained Delivery of Low-Dose IFN-alpha

Autores: Vasquez, M.; Consuegra-Fernandez, M.; Aranda, F. ; Jimenez, A. ; Tenesaca Cayambe, Shirley; Fernandez-Sendin, M. ; Gomar Peláez, Celia; Ardaiz Iriarte, Nuria María; Di Trani, C. A.; Casares Lagar, Noelia; Lasarte Sagastibelza, Juan José; Lozano, F. ; Berraondo López, Pedro (Autor de correspondencia)
Título de la revista: JOURNAL OF IMMUNOLOGY
ISSN: 0022-1767
Volumen: 203
Número: 3
Páginas: 696 - 704
Fecha de publicación: 2019
Multiple sclerosis (MS) is a chronic autoimmune disease with no curative treatment. The immune regulatory properties of type I IFNs have led to the approval of IFN-beta for the treatment of relapsing-remitting MS. However, there is still an unmet need to improve the tolerability and efficacy of this therapy. In this work, we evaluated the sustained delivery of IFN-alpha 1, either alone or fused to apolipoprotein A-1 by means of an adeno-associated viral (AAV) system in the mouse model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. These in vivo experiments demonstrated the prophylactic and therapeutic efficacy of the AAV-IFN-alpha or AAV-IFN-alpha fused to apolipoprotein A-1 vectors in experimental autoimmune encephalomyelitis, even at low doses devoid of hematological or neurologic toxicity. The sustained delivery of such low-dose IFN-alpha resulted in immunomodulatory effects, consisting of proinflammatory monocyte and T regulatory cell expansion. Moreover, encephalitogenic T lymphocytes from IFN-alpha-treated mice re-exposed to the myelin oligodendrocyte glycoprotein peptide in vitro showed a reduced proliferative response and cytokine (IL-17A and IFN-gamma) production, in addition to upregulation of immunosuppressive molecules, such as IL-10, IDO, or PD-1. In conclusion, the results of the present work support the potential of sustained delivery of low-dose IFN-alpha for the treatment of MS and likely other T cell-dependent chronic autoimmune disorders.