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  Notch-mediated generation of monocyte-derived Langerhans cells: Phenotype and function

Bellmann, L., Zelle-Rieser, C., Milne, P., Resteu, A., Tripp, C. H., Hermann-Kleiter, N., et al. (2020). Notch-mediated generation of monocyte-derived Langerhans cells: Phenotype and function. Journal of Investigative Dermatology. doi:10.1016/j.jid.2020.05.098.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-867A-A Version Permalink: http://hdl.handle.net/21.11116/0000-0006-867B-9
Genre: Journal Article

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 Creators:
Bellmann, Lydia, Author
Zelle-Rieser, Claudia, Author
Milne, Paul, Author
Resteu, Anastasia, Author
Tripp, Christoph H., Author
Hermann-Kleiter, Natascha, Author
Zaderer, Viktoria, Author
Wilflingseder, Doris, Author
Hörtnagl, Paul, Author
Theochari, Maria, Author
Schulze, Jessica1, Author              
Rentzsch, Mareike1, Author              
Del Frari, Barbara, Author
Collin, Matthew, Author
Rademacher, Christoph1, Author              
Romani, Nikolaus, Author
Stoitzner, Patrizia, Author
Affiliations:
1Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863300              

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 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/CD207 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 granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor (TGF)-β1 and the Notch ligand Delta-like 4 (DLL4) differentiate within 3 days into CD1a+Langerin+cells containing Birbeck granules. RNA-sequencing (RNA-seq) of these monocyte-derived LCs (moLCs) confirmed gene expression of LC-related molecules, pattern recognition receptors and enhanced expression of the antigen-presenting machinery. On 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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Language(s): eng - English
 Dates: 2020-06-06
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.jid.2020.05.098
Other: OA Liste?
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Title: Journal of Investigative Dermatology
Source Genre: Journal
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Publ. Info: New York, NY : Elsevier Science Pub. Co.
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 0022-202X