title: Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network.
abstract: Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin(+) cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10-20-fold. After the first week of life, we observed low-level proliferation of langerin(+) cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.
authors.affiliation: Centre for Molecular and Cellular Biology of Inflammation, Division of Immunobiology, Infection, and Inflammatory Diseases, King's College London, London SE1 1UL, England, UK.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chorro
authors.forename: Aurélien
authors.initials: A
authors.lastname: Sarde
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Woollard
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Barbaroux
authors.forename: Richard
authors.initials: R
authors.lastname: Groves
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000954:Antigens, Surface / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D003876:Dermatitis, Atopic / Q000473:pathology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D007801:Langerhans Cells / Q000502:physiology*; D037181:Lectins, C-Type / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D037241:Mannose-Binding Lectins / Q000032:analysis; D051379:Mice; D019707:Receptors, Chemokine / Q000502:physiology; D013234:Stem Cells / Q000502:physiology
chemical_list: D000954:Antigens, Surface; D000073883:CX3C Chemokine Receptor 1; C498497:Cd207 protein, mouse; C471885:Cx3cr1 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D019707:Receptors, Chemokine; D017493:Leukocyte Common Antigens