Notch-Mediated Generation of Monocyte-Derived Langerhans Cells: Phenotype and Function.

The Journal of Investigative Dermatology
Lydia BellmannPatrizia Stoitzner

Abstract

Langerhans cells (LCs) in the skin are a first line of defense against pathogens but also play an essential role in skin homeostasis. Their exclusive expression of the C-type lectin receptor Langerin makes them prominent candidates for immunotherapy. For vaccine testing, an easily accessible cell platform would be desirable as an alternative to the time-consuming purification of LCs from human skin. Here, we present such a model and demonstrate that monocytes in the presence of GM-CSF, TGF-β1, and the Notch ligand DLL4 differentiate within 3 days into CD1a+Langerin+cells containing Birbeck granules. RNA sequencing of these monocyte-derived LCs (moLCs) confirmed gene expression of LC-related molecules, pattern recognition receptors, and enhanced expression of genes involved in the antigen-presenting machinery. On the protein level, moLCs showed low expression of costimulatory molecules but prominent expression of C-type lectin receptors. MoLCs can be matured, secrete IL-12p70 and TNF-α, and stimulate proliferation and cytokine production in allogeneic CD4+ and CD8+ T cells. In regard to vaccine testing, a recently characterized glycomimetic Langerin ligand conjugated to liposomes demonstrated specific and fast internalization in...Continue Reading

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Citations

May 29, 2021·Frontiers in Chemistry·Dongyoon KimChristoph Rademacher

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Datasets Mentioned

BETA
GM-CSF
GSE141048

Methods Mentioned

BETA
Representative
electron microscopy
RNA-seq
flow cytometry
ELISA
density gradient centrifugation
PCR

Software Mentioned

Operetta Harmony
Operetta Imaging System
GraphPad Prism
ProcartaPlex
Operetta
FlowJo
Geneset

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