A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease
Daniel Korenfeld, … , Caroline Mann, Eynav Klechevsky
Daniel Korenfeld, … , Caroline Mann, Eynav Klechevsky
Published September 21, 2017
Citation Information: JCI Insight. 2017;2(18):e96101. https://doi.org/10.1172/jci.insight.96101.
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Research Article Immunology Inflammation

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

Abstract

Dendritic cells (DCs) are important in regulating immunity and tolerance and consist of functionally distinct subsets that differentially regulate T lymphocyte function. The underlying basis for this subset specificity is lacking, particularly in humans, where the classification of tissue DCs is currently incomplete. Examination of healthy human epidermal Langerhans cells and dermal skin cells revealed a tissue CD5-expressing DC subtype. The CD5+ DCs were potent inducers of cytotoxic T cells and Th22 cells. The products of these T cells, IL-22 and IFN-γ, play a key role in the pathogenesis of psoriasis. Remarkably, CD5+ DCs were significantly enriched in lesional psoriatic skin compared with distal tissues, suggesting their involvement in the disease. We show that CD5+ DCs can be differentiated from hematopoietic progenitor cells independently of the CD5– DCs. A progenitor population found in human cord blood and in the dermal skin layer, marked as CD34–CD123+CD117dimCD45RA+, was an immediate precursor of these CD11c+CD1c+CD5+ DCs. Overall, our discovery of the CD5-expressing DC subtype suggests that strategies to regulate their composition or function in the skin will represent an innovative approach for the treatment of immune-mediated disorders in and beyond the skin.

Authors

Daniel Korenfeld, Laurent Gorvel, Adiel Munk, Joshua Man, Andras Schaffer, Thomas Tung, Caroline Mann, Eynav Klechevsky

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Figure 7

CD34–CD123+CD117dimCD45RA+ cells preferentially give rise to CD5+ DCs.

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CD34–CD123+CD117dimCD45RA+ cells preferentially give rise to CD5+ DCs. (...
(A) Gating strategy for cord blood progenitors. Cells were sorted as Lin–DC–CD10–CD123– (see also Supplemental Figure 3): CD34+CD117+ (blue); CD34–CD117+ (orange); or Lin–DC–CD10–CD123+CD34–CD117dimCD45RA+ (red). Histograms show the expression of CD5 and CD45RA on the different progenitor subsets. Expression on lineage+ cells is shown as a control (gray). (B) Sorted cord blood CD34+CD123–CD117+, CD34−CD123–CD117–, or CD34−CD123+CD117dim progenitors were cultured in the presence of GM-CSF, SCF, FLT3-L, and LTα/β. Flow cytometry plots, gated on live CD45+HLA-DR+CD11c+ cells, show culture output of CD1a+CD5+ DCs on day 7. Representative results of 4 independent experiments are shown. (C) Gating strategy for dermal progenitors. Cells were sorted as Lin–DC–CD10– that were CD34+CD123–CD117– (blue); CD34–CD123–CD117+ (orange); or CD34−CD123+CD117dim (red). Histograms show the expression of CD5 and CD45RA on the different progenitor subsets. (D) CD34+CD123–CD117–, CD34−CD123–CD117+, or CD34−CD123+CD117dim were isolated from human dermis. Flow cytometry plots are gated on live CD45+HLA-DR+CD11c+ cells and show the expression of HLA-DR+ or lineage+ cells that were differentiated from the different progenitors. (E) The plots show the expression of CD1c and CD5 on HLA-DR+ cells that differentiated from CD34−CD123+CD117dim cells for 7 days in the presence of in the presence of GM-CSF (GM), SCF, and FLT3-L (FL) and either TNF-α or LTα/β. Representative results of 3 independent experiments are shown.