title: Langerin-expressing dendritic cells in human tissues are related to CD1c+ dendritic cells and distinct from Langerhans cells and CD141high XCR1+ dendritic cells.
abstract: Langerin is a C-type lectin expressed at high level by LCs of the epidermis. Langerin is also expressed by CD8(+)/CD103(+) XCR1(+) cross-presenting DCs of mice but is not found on the homologous human CD141(high) XCR1(+) myeloid DC. Here, we show that langerin is expressed at a low level on DCs isolated from dermis, lung, liver, and lymphoid tissue and that langerin(+) DCs are closely related to CD1c(+) myeloid DCs. They are distinguishable from LCs by the level of expression of CD1a, EpCAM, CD11b, CD11c, CD13, and CD33 and are found in tissues and tissue-draining LNs devoid of LCs. They are unrelated to CD141(high) XCR1(+) myeloid DCs, lacking the characteristic expression profile of cross-presenting DCs, conserved between mammalian species. Stem cell transplantation and DC deficiency models confirm that dermal langerin(+) DCs have an independent homeostasis to LCs. Langerin is not expressed by freshly isolated CD1c(+) blood DCs but is rapidly induced on CD1c(+) DCs by serum or TGF-β via an ALK-3-dependent pathway. These results show that langerin is expressed outside of the LC compartment of humans and highlight a species difference: langerin is expressed by the XCR1(+) "DC1" population of mice but is restricted to the CD1c(+) "DC2" population of humans (homologous to CD11b(+) DCs in the mouse).
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: McGovern
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Milne
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dickinson
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pagan
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cookson
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.affiliation: Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom matthew.collin@ncl.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D018949:Antigens, CD1 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000037:antagonists & inhibitors / Q000502:physiology; D003713:Dendritic Cells / Q000737:chemistry / Q000145:classification* / Q000187:drug effects; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000032:analysis*; D006706:Homeostasis; D006801:Humans; D007801:Langerhans Cells / Q000145:classification; D037181:Lectins, C-Type / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008221:Lymphoid Tissue / Q000166:cytology; D037241:Mannose-Binding Lectins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009928:Organ Specificity; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D044967:Serum; D012867:Skin / Q000166:cytology; D018180:Thrombomodulin; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D000943:Antigens, Differentiation; D000954:Antigens, Surface; C437944:CD1C protein, human; C121916:CD207 protein, human; C498497:Cd207 protein, mouse; D006023:Glycoproteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D043562:Receptors, G-Protein-Coupled; C546931:THBD protein, human; D018180:Thrombomodulin; D016212:Transforming Growth Factor beta; C091671:XCR1 protein, human; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: DCML deficiency; GATA2; HSCT; antigen presenting cell; differentiation