PMID- 24352044 OWN - NLM STAT- MEDLINE DCOM- 20140527 LR - 20221109 IS - 1523-1747 (Electronic) IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 134 IP - 4 DP - 2014 Apr TI - A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels. PG - 965-974 LID - S0022-202X(15)36703-8 [pii] LID - 10.1038/jid.2013.481 [doi] AB - Dendritic cells (DCs), macrophages (Mphi), 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(+) Mphi, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mphi. DCs formed the first dermal cellular layer (0-20 mum beneath the dermoepidermal junction), Mphi were located deeper (40-60 mum), and CD3(+) lymphocytes were observed throughout (0-60 mum). Below this level, DCs, T cells, and the majority of Mphi 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 mum) 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 Mphi 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. FAU - Wang, Xiao-Nong AU - Wang XN AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - McGovern, Naomi AU - McGovern N AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - Gunawan, Merry AU - Gunawan M AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - Richardson, Connor AU - Richardson C AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - Windebank, Martin AU - Windebank M AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - Siah, Tee-Wei AU - Siah TW AD - Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. FAU - Lim, Hwee-Ying AU - Lim HY AD - National University of Singapore, Singapore, Singapore. FAU - Fink, Katja AU - Fink K AD - Singapore Immunology Network, A*Star, Singapore, Singapore. FAU - Yao Li, Jackson L AU - Yao Li JL AD - Singapore Immunology Network, A*Star, Singapore, Singapore. FAU - Ng, Lai G AU - Ng LG AD - Singapore Immunology Network, A*Star, Singapore, Singapore. FAU - Ginhoux, Florent AU - Ginhoux F AD - Singapore Immunology Network, A*Star, Singapore, Singapore. FAU - Angeli, Veronique AU - Angeli V AD - National University of Singapore, Singapore, Singapore. FAU - Collin, Matthew AU - Collin M AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. FAU - Haniffa, Muzlifah AU - Haniffa M AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: m.a.haniffa@ncl.ac.uk. LA - eng GR - Wellcome Trust/United Kingdom GR - 088555/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131111 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (CD11c Antigen) RN - 0 (Carrier Proteins) RN - 0 (Microfilament Proteins) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 146808-54-0 (fascin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Anisotropy MH - CD11c Antigen/metabolism MH - Carrier Proteins/metabolism MH - Cell Movement MH - Dermis/blood supply/cytology/pathology MH - Female MH - Flow Cytometry MH - Humans MH - Langerhans Cells/cytology MH - Leukocytes/*cytology MH - Lymphatic System MH - Lymphatic Vessels/pathology MH - Lymphocytes/cytology/metabolism MH - Lymphoma, T-Cell, Cutaneous/metabolism MH - Macrophages/*cytology/*pathology MH - Microfilament Proteins/metabolism MH - Middle Aged MH - Phenotype MH - Platelet Endothelial Cell Adhesion Molecule-1/metabolism MH - Skin/*blood supply/*cytology/pathology MH - Young Adult PMC - PMC3961477 MID - EMS55583 OID - NLM: EMS55583 EDAT- 2013/12/20 06:00 MHDA- 2014/05/28 06:00 CRDT- 2013/12/20 06:00 PHST- 2013/06/16 00:00 [received] PHST- 2013/09/25 00:00 [revised] PHST- 2013/10/02 00:00 [accepted] PHST- 2013/12/20 06:00 [entrez] PHST- 2013/12/20 06:00 [pubmed] PHST- 2014/05/28 06:00 [medline] AID - S0022-202X(15)36703-8 [pii] AID - 10.1038/jid.2013.481 [doi] PST - ppublish SO - J Invest Dermatol. 2014 Apr;134(4):965-974. doi: 10.1038/jid.2013.481. Epub 2013 Nov 11.