Regulation of dendritic cell differentiation and function by Notch and Wnt pathways

Abstract

The process of dendritic cell differentiation is governed by a tightly controlled signaling network regulated by cytokines and direct interaction between progenitor cells and bone marrow stroma. Notch signaling represents one of the major pathways activated during direct interaction between hematopoietic progenitor cells and bone marrow stroma. Wnt pathway is activated by soluble proteins produced by bone marrow stroma. Until recently, the role of Notch and Wnt signaling in the development of myeloid cells and dendritic cells in particular remained unclear. In this review, we discuss recent exciting findings that shed light on the critical role of Notch and Wnt pathways, their interaction in differentiation and function of dendritic cells, and their impact on immune responses.

MicroRNAs Regulate Dendritic Cell Differentiation and Function

“…Notch/Wnt signaling is important in DC development (41), and this pathway can be influenced by miRNA action. Hashimi et al (34) analyzed miRNA expression profiles in human monocyte-derived DCs (MDDC) over multiple days of differentiation and identified miR-21 and miR-34a as being of interest.…”

Ligation of Notch Receptors in Human Conventional and Plasmacytoid Dendritic Cells Differentially Regulates Cytokine and Chemokine Secretion and Modulates Th Cell Polarization

“…The presence of Notch receptors and ligands has been widely described in mice (macrophages, thymic DCs, splenic DCs, bone marrow-derived DCs) and human myeloid cells (macrophages and monocyte-derived DCs) (reviewed in Ref. 32) and in mouse splenic pDCs (33). Only one study has reported the expression of Notch molecules in human BDCA1…”

“…Cellular activation alters the expression of Notch molecules on DCs, which modifies Th cell polarization (32,35,36). Additionally, Notch signaling itself is also involved in activation of DCs, as ligand binding induced upregulation of MHC class II (MHC-II), CD80, CD83, and CD86, production of different cytokines, and higher levels of T cell proliferation (37)(38)(39).…”

Transcriptional priming of intrathymic precursors for dendritic cell development

“…The latent DC potential in the thymus has, furthermore, been revealed by conditional ablation of Notch1, which increases DN1c cells and DCs in the thymus (Feyerabend et al, 2009;Radtke et al, 2000). However, other experiments have suggested that a more complex relationship exists between Notch signaling and DC development (Cheng et al, 2010). In mammals, there are four Notch receptors, Notch1, -2, -3 and -4, and five Notch ligands, Delta-like-1 (Dll1), Dll3, Dll4, Jagged 1 and Jagged 2 (Yuan et al, 2010).…”