title: Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes.
abstract: Langerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. We found that, in contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103(+)CD11b(lo) (CD103(+)) and CD11b(+)CD103(-) (CD11b(+)) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103(+) LCs originate from pre-DCs, whereas CD11b(+) LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, the transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with the epithelial position, morphology, and expression of the LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DC, and monocytic) in steady state.
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Capucha
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mizraji
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Segev
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Blecher-Gonen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Winter
authors.affiliation: General Surgery Department, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Abed
authors.initials: A
authors.lastname: Khalaileh
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Tabib
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Tsipora
authors.initials: T
authors.lastname: Attal
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Maria
authors.initials: M
authors.lastname: Nassar
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Katya
authors.initials: K
authors.lastname: Zelentsova
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Hen
authors.initials: H
authors.lastname: Kisos
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Seré
authors.affiliation: Institute for Biomedical Engineering, Department of Cell Biology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hieronymus
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Burstyn-Cohen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Department of Periodontology, Faculty of Dental Medicine, Hadassah Medical Center, Jerusalem 91120, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Wilensky
authors.affiliation: Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Hadassah, Jerusalem 91120, Israel. Electronic address: avihaih@ekmd.huji.ac.il.
authors.forename: Avi-Hai
authors.initials: AH
authors.lastname: Hovav
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001775:Blood Circulation; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004848:Epithelium / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D009061:Mouth Mucosa / Q000276:immunology*; D009928:Organ Specificity; D012867:Skin / Q000276:immunology; D059467:Transcriptome / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D039481:CD11b Antigen; C498497:Cd207 protein, mouse; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C091367:alpha E integrins