Bellmann L

Collin M

Del Frari B

Hermann-Kleiter N

Hortnagl P

Milne P

Rademacher C

Rentzsch M

Resteu A

Romani N

Schulze J

Stoitzner P

Theochari M

Tripp CH

Wilflingseder D

Zaderer V

Zelle-Rieser C

\ua9 2020 The Authors. 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 into moLCs. Hence, these short-term in vitro‒generated moLCs represent an interesting tool to screen LC-based vaccines in the future

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

https://eprint.ncl.ac.uk/file_store/production/271060/6D186D05-9A09-4EC4-AD3A-8FE973779A91.pdf

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

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