title: The clash of Langerhans cell homeostasis in skin: Should I stay or should I go?
abstract: Langerhans cells (LC), the skin epidermal contingent of dendritic cells (DC), possess an exceptional life cycle and developmental origin. LC, like all mature blood cells, develop from haematopoietic stem cells (HSC) through successive steps of lineage commitment and differentiation. However, LC development is different to that of other DC subsets and not yet fully understood. Haematopoietic cell fate decisions are instructed by specific growth factors and cytokines produced in specialized microenvironments or niches. Upon ligand binding the cognate surface receptors on HSC and further restricted progenitor cells regulate the signalling pathways that eventually leads to the execution of lineage-determining genetic programs. In this review we focus on a specific set of surface receptor kinases that have been identified as critical regulators of LC development using genetically modified mice. Recent studies suggest for some of these kinases to impact on LC/LC progenitor interaction with the local niche by regulating adhesion and/or migration. During embryonic development, in wound healing and aberrantly in tumour invasion the same kinase receptors control a genetic program known as epithelial-to-mesenchymal-transition (EMT). We will discuss how EMT and its reverse program of mesenchymal-to-epithelial-transition (MET) can serve as universal concepts operating also in LC development.
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. Electronic address: thomas.hieronymus@rwth-aachen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hieronymus
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Jea-Hyun
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Seré
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D020794:Receptor Protein-Tyrosine Kinases
keywords: Dendritic cell; Epithelial-to-mesenchymal-transition; Langerhans cell; Met-signalling; Receptor tyrosine kinase; TGF-β-signalling