The canonical BMP signaling pathway is involved in human monocyte-derived dendritic cell maturation.
Immunol Cell Biol
; 89(5): 610-8, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21102536
ABSTRACT
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-ß superfamily, are multifunctional polypeptides regulating a broad spectrum of functions in embryonic and adult tissues. Recent reports have demonstrated that BMPs regulate the survival, proliferation and differentiation of several cell types in the immune system. In this study, we investigate the effects of BMP signaling activation on the capacity of human dendritic cells (DCs) to stimulate immune responses. Human DCs express type I and type II BMP receptors (BMPRIA, BMPRIB, type IA activin receptor, BMPRII) and BMP signal transduction molecules (Smad1, 5, and 8, as well as Smad4). On BMP stimulation, Id1-3 (inhibitor of differentiation 1-3/DNA binding) mRNA expression is upregulated and this effect can be blocked with the inhibitor dorsomorphin, showing that the canonical BMP signal transduction pathway is functionally active in DCs. BMP signaling activation promotes the phenotypic maturation of human DCs by increasing the expression of co-stimulatory molecules and also CD83, programmed cell death ligand 1 (PD-L1) and PD-L2, and stimulates cytokine secretion, mainly interleukin-8 and tumor necrosis factor-α. Accordingly, BMP-treated DCs exhibit an enhanced T-cell stimulatory capacity. BMP signaling also enhances the survival of human DCs increasing the Bcl-2/Bax ratio. Finally, the expression of Runx transcription factors is increased in mature DCs, and the mRNA levels of Runx1-3 are upregulated in response to BMP stimulation, indicating that Runx transcription factor family may mediate the effects of BMP signaling in human DC maturation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Monocitos
/
Proteínas Morfogenéticas Óseas
Límite:
Humans
Idioma:
En
Revista:
Immunol Cell Biol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
España