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

Alfonso Rodríguez-Gil*, Virginia Escamilla-Gómez, Melanie Nufer, Félix Andújar-Sánchez, Teresa Lopes-Ramos, José Antonio Bejarano-García, Estefanía García-Guerrero, Cristina Calderón-Cabrera, Teresa Caballero-Velázquez, Clara Beatriz García-Calderón, Paola Hernández-Díaz, Juan Luis Reguera-Ortega, Nancy Rodríguez-Torres, Nuria Martínez-Cibrián, José Ignacio Rodríguez-Barbosa, Javier Villadiego, José Antonio Pérez-Simón

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

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 effect in the treatment of GvHD. For this purpose, we studied the effect 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 affecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efficacy 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 effect. This beneficial effect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer.

Original languageEnglish
Article number8348
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 19 May 2022
Externally publishedYes

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