Functional Role of P-Selectin Glycoprotein Ligand 1/P-Selectin Interaction in the Generation of Tolerogenic Dendritic Cells

Dendritic cells (DCs) have a key role in both the generation of the immune response and the induction of tolerance to self-Ags. In this work, the possible role of P-selectin glycoprotein ligand 1 (PSGL-1) on the tolerogenic activity of human DCs was explored. We found that the engagement of PSGL-1 b...

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Detalhes bibliográficos
Autores: Urzainqui, Ana, Martínez del Hoyo, Gloria, Lamana Domínguez, Amalia, Fuente, Hortensia de la, Barreiro, Olga, Olazabal, Isabel, Pilar Martin, Wild, Martin, Vestweber, Dietmar, González-Amaro, Roberto, Sánchez-Madrid, Francisco
Formato: artículo
Fecha de publicación:2007
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/94052
Acesso em linha:https://hdl.handle.net/20.500.14352/94052
Access Level:acceso abierto
Palavra-chave:576.3
577.27
P-Selectin Glycoprotein Ligand 1
Dendritic Cells
Biología celular (Biología)
Inmunología
2407 Biología Celular
2412 Inmunología
Descrição
Resumo:Dendritic cells (DCs) have a key role in both the generation of the immune response and the induction of tolerance to self-Ags. In this work, the possible role of P-selectin glycoprotein ligand 1 (PSGL-1) on the tolerogenic activity of human DCs was explored. We found that the engagement of PSGL-1 by P-selectin on DCs induced the expression of c-Fos, IDO, IL-10, and TGF-β genes. Remarkably, stimulation of DCs through PSGL-1 with P-selectin enhanced their capability to generate CD4+CD25+Foxp3+ regulatory T cells, which expressed high levels of TGF-β1 mRNA, synthesized IL-10, and suppressed the proliferation of autologous CD4+CD25− T cells. Accordingly, we found that DCs from PSGL-1−/− mice expressed higher levels of MHC class II molecules, and exhibited an enhanced immunogenicity compared with wild-type mice. In addition, the percentage of CD4+CD25+Foxp3+ regulatory T cells in the thymus of PSGL-1-deficient animals was significantly reduced. Our data reveal an unexpected role of PSGL-1 on the tolerogenic function of DCs, and the regulation of the immune response.