Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib

Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic efect...

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Detalles Bibliográficos
Autores: Rodríguez Gil, Alfonso, Escamilla Gómez, Virginia, Nufer, Melanie, Andújar Sánchez, Félix, Lopes Ramos, Teresa, Bejarano García, José Antonio, Caballero Velázquez, Teresa, Villadiego Luque, Francisco Javier, Pérez Simón, José Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/139859
Acceso en línea:https://hdl.handle.net/11441/139859
https://doi.org/10.1038/s41598-022-12407-x
Access Level:acceso abierto
Palabra clave:Graft versus host disease
Regulatory T cells
Ruxolitinib
Descripción
Sumario:Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic efect in the treatment of GvHD. For this purpose, we studied the efect of this combination both in vitro and in a GvHD mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T cells to conventional T cells in culture, without afecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efcacy as compared to each single treatment alone in our GvHD mouse model in terms of GvHD incidence, severity and survival without hampering graft versus leukemia efect. This benefcial efect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer.