title: A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels.
abstract: Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mφ, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mφ. DCs formed the first dermal cellular layer (0-20 μm beneath the dermoepidermal junction), Mφ were located deeper (40-60 μm), and CD3(+) lymphocytes were observed throughout (0-60 μm). Below this level, DCs, T cells, and the majority of Mφ formed stable perivascular sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes previously underestimated from cross-section views. The total area of apical dermis (0-30 μm) contained approximately 10-fold more myeloid DCs than the entire blood volume of an average individual. Surprisingly, <1% of dermal DCs occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated within lymphatics, but Mφ remained fixed in skin explants cultured ex vivo. The leukocyte architecture observed in normal skin was distorted in inflammation and disease. These studies illustrate the micro-anatomy of dermal leukocytes and provide further insights into their functional organization.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Xiao-Nong
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: McGovern
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Merry
authors.initials: M
authors.lastname: Gunawan
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Connor
authors.initials: C
authors.lastname: Richardson
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Windebank
authors.affiliation: Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
authors.forename: Tee-Wei
authors.initials: TW
authors.lastname: Siah
authors.affiliation: National University of Singapore, Singapore, Singapore.
authors.forename: Hwee-Ying
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Singapore Immunology Network, A*Star, Singapore, Singapore.
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
authors.affiliation: Singapore Immunology Network, A*Star, Singapore, Singapore.
authors.forename: Jackson L
authors.initials: JL
authors.lastname: Yao Li
authors.affiliation: Singapore Immunology Network, A*Star, Singapore, Singapore.
authors.forename: Lai G
authors.initials: LG
authors.lastname: Ng
authors.affiliation: Singapore Immunology Network, A*Star, Singapore, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: National University of Singapore, Singapore, Singapore.
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: m.a.haniffa@ncl.ac.uk.
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016880:Anisotropy; D039521:CD11c Antigen / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement; D020405:Dermis / Q000098:blood supply / Q000166:cytology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology; D007962:Leukocytes / Q000166:cytology*; D008208:Lymphatic System; D042601:Lymphatic Vessels / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000473:pathology*; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012867:Skin / Q000098:blood supply* / Q000166:cytology* / Q000473:pathology; D055815:Young Adult
chemical_list: D039521:CD11c Antigen; D002352:Carrier Proteins; D008840:Microfilament Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C020324:fascin