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

Lookup NU author(s): Dr Paul Milne, Dr Anastasia Resteu, Professor Matthew Collin

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

Author(s): Bellmann L, Zelle-Rieser C, Milne P, Resteu A, Tripp CH, Hermann-Kleiter N, Zaderer V, Wilflingseder D, Hortnagl P, Theochari M, Schulze J, Rentzsch M, Del Frari B, Collin M, Rademacher C, Romani N, Stoitzner P

Publication type: Article

Publication status: Published

Journal: Journal of Investigative Dermatology

Year: 2021

Volume: 141

Issue: 1

Pages: 84-94.e6

Print publication date: 01/01/2021

Online publication date: 05/06/2020

Acceptance date: 04/05/2020

Date deposited: 09/12/2020

ISSN (print): 0022-202X

ISSN (electronic): 1523-1747

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.jid.2020.05.098

DOI: 10.1016/j.jid.2020.05.098

PubMed id: 32522485


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