title: The canonical BMP signaling pathway is involved in human monocyte-derived dendritic cell maturation.
abstract: Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β 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.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Martínez
authors.forename: Carmen
authors.initials: C
authors.lastname: Hernández-López
authors.forename: Jaris
authors.initials: J
authors.lastname: Valencia
authors.forename: Laura
authors.initials: L
authors.lastname: Hidalgo
authors.forename: Ana
authors.initials: A
authors.lastname: Entrena
authors.forename: Agustín G
authors.initials: AG
authors.lastname: Zapata
authors.forename: Angeles
authors.initials: A
authors.lastname: Vicente
authors.forename: Rosa
authors.initials: R
authors.lastname: Sacedón
authors.forename: Alberto
authors.initials: A
authors.lastname: Varas
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050657:Core Binding Factor alpha Subunits / Q000235:genetics; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019485:Bone Morphogenetic Proteins; D050657:Core Binding Factor alpha Subunits; D016207:Cytokines; D012333:RNA, Messenger