title: Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.
abstract: Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain. Mice lacking IL-34 displayed a marked reduction of LCs and a decrease of microglia, whereas monocytes, dermal, and lymphoid tissue macrophages and DCs were unaffected. We identified IL-34 as a nonredundant cytokine for the development of LCs during embryogenesis as well as for their homeostasis in the adult skin. Whereas inflammation-induced repopulation of LCs appears to be dependent on Csf-1, once inflammation is resolved, LC survival is again IL-34-dependent. In contrast, microglia and their yolk sac precursors develop independently of IL-34 but rely on it for their maintenance in the adult brain.
authors.affiliation: Institute of Experimental Immunology, Neuroimmunology, University of Zürich, CH 8006 Zürich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Greter
authors.affiliation: Institute of Experimental Immunology, Neuroimmunology, University of Zürich, CH 8006 Zürich, Switzerland.
authors.forename: Iva
authors.initials: I
authors.lastname: Lelios
authors.affiliation: Institute of Laboratory Animal Science, University of Zürich, CH 8006 Zürich, Switzerland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Pelczar
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), BIOPOLIS, 138648, Singapore.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoeffel
authors.affiliation: Department of Oncological Sciences, New York, NY 10029, USA.|The Immunology Institute, New York, NY 10029, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Price
authors.affiliation: Department of Oncological Sciences, New York, NY 10029, USA.|The Immunology Institute, New York, NY 10029, USA.
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.affiliation: Clinical Tumor Biology & Immunotherapy Unit, University Hospital Zürich, 8091 Zürich, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.affiliation: Department of Neurosurgery, University Hospital Zürich, 8091 Zürich, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Frei
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), BIOPOLIS, 138648, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Department of Oncological Sciences, New York, NY 10029, USA.|The Immunology Institute, New York, NY 10029, USA.|Tisch Cancer Institute Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Institute of Experimental Immunology, Neuroimmunology, University of Zürich, CH 8006 Zürich, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; C552364:interleukin-34, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor