Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis

Accumulating evidence on the role of Thrombospondin-1 (TSP-1) in the immune response has emerged during the last years. In spite of the importance of TSP-1 not only as anti-angiogenic factor but also as an immunomodulatory molecule, studies on the role of TSP-1 in psoriasis have been neglected. TSP-...

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Autores: Rodríguez Jiménez, Pedro Antonio, Chicharro Manso, Pablo, Llamas Velasco, María del Mar, Cibrian, Danay, Trigo Torres, Laura, Vara, Alicia, Jiménez Fernández, María, Sevilla Montero, Javier, Calzada García, María Josefa, Sánchez Madrid, Francisco, Fuente, Hortensia de la, Daudén Tello, Esteban
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/690637
Acceso en línea:http://hdl.handle.net/10486/690637
https://dx.doi.org/10.3389/fimmu.2019.01268
Access Level:acceso abierto
Palabra clave:psoriasis
CD47
TSP-1
Th17
Treg cells
Medicina
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spelling Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasisRodríguez Jiménez, Pedro AntonioChicharro Manso, PabloLlamas Velasco, María del MarCibrian, DanayTrigo Torres, LauraVara, AliciaJiménez Fernández, MaríaSevilla Montero, JavierCalzada García, María JosefaSánchez Madrid, FranciscoFuente, Hortensia de laDaudén Tello, EstebanpsoriasisCD47TSP-1Th17Treg cellsMedicinaAccumulating evidence on the role of Thrombospondin-1 (TSP-1) in the immune response has emerged during the last years. In spite of the importance of TSP-1 not only as anti-angiogenic factor but also as an immunomodulatory molecule, studies on the role of TSP-1 in psoriasis have been neglected. TSP-1 and CD47 expression were analyzed in skin samples from psoriasis patients and control subjects using RT-PCR and immunofluorescence. Expression of these molecules was also evaluated in peripheral blood CD4+ T cells, moDCs, and circulating primary DCs. The functional role of TSP-1/CD47 signaling axis in psoriasis was assessed in Th17 and Treg differentiation assays. Additionally, small interfering RNA assays specific to TSP-1 were performed in CD4+ T cells and monocyte derived DC to specifically evaluate the function of this protein. Lesional skin of psoriasis patients expressed lower TSP-1 and CD47 mRNA levels compared to non-lesional skin or skin from controls. Immunofluorescence staining revealed decreased expression of CD47 in CD45+ dermal cells from psoriasis samples compared to control subjects. Peripheral CD4+ T cells and circulating primary DCs from psoriasis also expressed lower levels of CD47 compared to controls. Although no significant differences were detected in TSP-1 expression in CD4+ T cells and moDCs between patients and controls, TSP-1 expression in psoriasis patients inversely correlated with disease activity evaluated by the Psoriasis Area and Index Activity. Furthermore, exogenous TSP-1 inhibited Th17 differentiation and stimulated the differentiation of CD4+ T cells toward Treg cells. Furthermore, RNA interference specific for TSP-1 confirmed the role of this molecule as a negative regulator of T cell activation. Because of the impact of TSP-1/CD47 signaling axis in Th17 and Treg differentiation, a dysregulated expression of these molecules in the immune cells from psoriasis patients may favor the exacerbated inflammatory response in this diseaseInstituto de Salud Carlos III (AES 2017): PI17/01972 to ED. Janssen; Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV); Proyecto Integrado de Excelencia PIE13/00041, Instituto de Salud Carlos III to FS-M, Instituto de Salud Carlos III PI16/02166, Universidad Autónoma de Madrid-Banco Santander (grant 2017/EEUU/03), and Red Temática de Excelencia en Investigación en Hipoxia (SAF 2017-90794-REDT) to MJC. This research has been co-financed by Fondo Europeo de Desarrollo Regional (FEDER)Frontiers MediaDepartamento de MedicinaFacultad de Medicina20192019-06-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/690637https://dx.doi.org/10.3389/fimmu.2019.01268reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6906372026-06-23T12:46:27Z
dc.title.none.fl_str_mv Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
title Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
spellingShingle Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
Rodríguez Jiménez, Pedro Antonio
psoriasis
CD47
TSP-1
Th17
Treg cells
Medicina
title_short Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
title_full Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
title_fullStr Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
title_full_unstemmed Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
title_sort Thrombospondin-1/CD47 interaction regulates Th17 and treg differentiation in psoriasis
dc.creator.none.fl_str_mv Rodríguez Jiménez, Pedro Antonio
Chicharro Manso, Pablo
Llamas Velasco, María del Mar
Cibrian, Danay
Trigo Torres, Laura
Vara, Alicia
Jiménez Fernández, María
Sevilla Montero, Javier
Calzada García, María Josefa
Sánchez Madrid, Francisco
Fuente, Hortensia de la
Daudén Tello, Esteban
author Rodríguez Jiménez, Pedro Antonio
author_facet Rodríguez Jiménez, Pedro Antonio
Chicharro Manso, Pablo
Llamas Velasco, María del Mar
Cibrian, Danay
Trigo Torres, Laura
Vara, Alicia
Jiménez Fernández, María
Sevilla Montero, Javier
Calzada García, María Josefa
Sánchez Madrid, Francisco
Fuente, Hortensia de la
Daudén Tello, Esteban
author_role author
author2 Chicharro Manso, Pablo
Llamas Velasco, María del Mar
Cibrian, Danay
Trigo Torres, Laura
Vara, Alicia
Jiménez Fernández, María
Sevilla Montero, Javier
Calzada García, María Josefa
Sánchez Madrid, Francisco
Fuente, Hortensia de la
Daudén Tello, Esteban
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv psoriasis
CD47
TSP-1
Th17
Treg cells
Medicina
topic psoriasis
CD47
TSP-1
Th17
Treg cells
Medicina
description Accumulating evidence on the role of Thrombospondin-1 (TSP-1) in the immune response has emerged during the last years. In spite of the importance of TSP-1 not only as anti-angiogenic factor but also as an immunomodulatory molecule, studies on the role of TSP-1 in psoriasis have been neglected. TSP-1 and CD47 expression were analyzed in skin samples from psoriasis patients and control subjects using RT-PCR and immunofluorescence. Expression of these molecules was also evaluated in peripheral blood CD4+ T cells, moDCs, and circulating primary DCs. The functional role of TSP-1/CD47 signaling axis in psoriasis was assessed in Th17 and Treg differentiation assays. Additionally, small interfering RNA assays specific to TSP-1 were performed in CD4+ T cells and monocyte derived DC to specifically evaluate the function of this protein. Lesional skin of psoriasis patients expressed lower TSP-1 and CD47 mRNA levels compared to non-lesional skin or skin from controls. Immunofluorescence staining revealed decreased expression of CD47 in CD45+ dermal cells from psoriasis samples compared to control subjects. Peripheral CD4+ T cells and circulating primary DCs from psoriasis also expressed lower levels of CD47 compared to controls. Although no significant differences were detected in TSP-1 expression in CD4+ T cells and moDCs between patients and controls, TSP-1 expression in psoriasis patients inversely correlated with disease activity evaluated by the Psoriasis Area and Index Activity. Furthermore, exogenous TSP-1 inhibited Th17 differentiation and stimulated the differentiation of CD4+ T cells toward Treg cells. Furthermore, RNA interference specific for TSP-1 confirmed the role of this molecule as a negative regulator of T cell activation. Because of the impact of TSP-1/CD47 signaling axis in Th17 and Treg differentiation, a dysregulated expression of these molecules in the immune cells from psoriasis patients may favor the exacerbated inflammatory response in this disease
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-06-04
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/690637
https://dx.doi.org/10.3389/fimmu.2019.01268
url http://hdl.handle.net/10486/690637
https://dx.doi.org/10.3389/fimmu.2019.01268
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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