Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control
Producción Científica
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Valladolid |
| Repositorio: | UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| OAI Identifier: | oai:uvadoc.uva.es:10324/55160 |
| Acceso en línea: | https://doi.org/10.1111/bjh.13984 https://uvadoc.uva.es/handle/10324/55160 |
| Access Level: | acceso abierto |
| Palabra clave: | Graft versus host disease Cell transplantation Trasplante de células Pharmacology MTOR inhibitors 3205.04 Hematología 3201.01 Oncología |
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Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease controlHerrero Sánchez, María del CarmenRodríguez Serrano, ConcepciónAlmeida Parra, JuliaSan Segundo Payo, LauraInogés Sancho, LauraSantos-Briz Terrón, ÁngelGarcía Briñón, JesúsSan Miguel Izquierdo, Jesús F.Cañizo Fernández-Roldán, Consuelo delBlanco Durango, BelénGraft versus host diseaseCell transplantationTrasplante de célulasPharmacologyMTOR inhibitors3205.04 Hematología3201.01 OncologíaProducción CientíficaThe mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting na€ıve T cell activation and the expression of Tcell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.Gerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13)John Wiley & Sons2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1111/bjh.13984https://uvadoc.uva.es/handle/10324/55160reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://onlinelibrary.wiley.com/doi/10.1111/bjh.13984info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:uvadoc.uva.es:10324/551602026-06-13T12:44:47Z |
| dc.title.none.fl_str_mv |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| title |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| spellingShingle |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control Herrero Sánchez, María del Carmen Graft versus host disease Cell transplantation Trasplante de células Pharmacology MTOR inhibitors 3205.04 Hematología 3201.01 Oncología |
| title_short |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| title_full |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| title_fullStr |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| title_full_unstemmed |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| title_sort |
Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control |
| dc.creator.none.fl_str_mv |
Herrero Sánchez, María del Carmen Rodríguez Serrano, Concepción Almeida Parra, Julia San Segundo Payo, Laura Inogés Sancho, Laura Santos-Briz Terrón, Ángel García Briñón, Jesús San Miguel Izquierdo, Jesús F. Cañizo Fernández-Roldán, Consuelo del Blanco Durango, Belén |
| author |
Herrero Sánchez, María del Carmen |
| author_facet |
Herrero Sánchez, María del Carmen Rodríguez Serrano, Concepción Almeida Parra, Julia San Segundo Payo, Laura Inogés Sancho, Laura Santos-Briz Terrón, Ángel García Briñón, Jesús San Miguel Izquierdo, Jesús F. Cañizo Fernández-Roldán, Consuelo del Blanco Durango, Belén |
| author_role |
author |
| author2 |
Rodríguez Serrano, Concepción Almeida Parra, Julia San Segundo Payo, Laura Inogés Sancho, Laura Santos-Briz Terrón, Ángel García Briñón, Jesús San Miguel Izquierdo, Jesús F. Cañizo Fernández-Roldán, Consuelo del Blanco Durango, Belén |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Graft versus host disease Cell transplantation Trasplante de células Pharmacology MTOR inhibitors 3205.04 Hematología 3201.01 Oncología |
| topic |
Graft versus host disease Cell transplantation Trasplante de células Pharmacology MTOR inhibitors 3205.04 Hematología 3201.01 Oncología |
| description |
Producción Científica |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://doi.org/10.1111/bjh.13984 https://uvadoc.uva.es/handle/10324/55160 |
| url |
https://doi.org/10.1111/bjh.13984 https://uvadoc.uva.es/handle/10324/55160 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://onlinelibrary.wiley.com/doi/10.1111/bjh.13984 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
John Wiley & Sons |
| publisher.none.fl_str_mv |
John Wiley & Sons |
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reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid instname:Universidad de Valladolid |
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Universidad de Valladolid |
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UVaDOC. Repositorio Documental de la Universidad de Valladolid |
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UVaDOC. Repositorio Documental de la Universidad de Valladolid |
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1869417786051133440 |
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15,300719 |