TY - JOUR
T1 - A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels
AU - Wang, Xiao Nong
AU - McGovern, Naomi
AU - Gunawan, Merry
AU - Richardson, Connor
AU - Windebank, Martin
AU - Siah, Tee Wei
AU - Lim, Hwee Ying
AU - Fink, Katja
AU - Li, Jackson L.Yao
AU - Ng, Lai G.
AU - Ginhoux, Florent
AU - Angeli, Veronique
AU - Collin, Matthew
AU - Haniffa, Muzlifah
N1 - Funding Information:
This study was funded by the Wellcome Trust (WT088555) and Tyneside Leukaemia Research Association. We thank Dr Trevor Booth and Dr Alex Laude for bio-imaging, Dr Xin Xu for tissue processing, and the support of Professor Peter Farr, Dr Sophie Weatherhead, Dr John Frew, Dr Clifford Lawrence, and Dr Khadija Al-Jefri from the Department of Dermatology and Oncology, Newcastle upon Tyne NHS Trust.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84897095935&partnerID=8YFLogxK
U2 - 10.1038/jid.2013.481
DO - 10.1038/jid.2013.481
M3 - Article
C2 - 24352044
AN - SCOPUS:84897095935
SN - 0022-202X
VL - 134
SP - 965
EP - 974
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -