title: Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation.
abstract: IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio-temporal production of IL-34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34(LacZ) reporter mice and newly generated inducible Il34-knockout mice. We found that IL-34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL-34 to continually self-renew in the steady state. However, during UV-induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL-34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil-derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes.
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Brescia, Brescia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bugatti
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Tyler K
authors.initials: TK
authors.lastname: Ulland
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.|Department of Pathology, University of Brescia, Brescia, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.affiliation: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015603:Keratinocytes / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: D007378:Interleukins; C552364:interleukin-34, mouse; D016173:Macrophage Colony-Stimulating Factor
keywords: CSF1; Cell development; Cytokines; IL-34; Inflammation langerhans cells