A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease
Daniel Korenfeld, Laurent Gorvel, Adiel Munk, Joshua Man, Andras Schaffer, Thomas Tung, Caroline Mann, Eynav Klechevsky
Daniel Korenfeld, Laurent Gorvel, Adiel Munk, Joshua Man, Andras Schaffer, Thomas Tung, Caroline Mann, Eynav Klechevsky
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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 4

Functional characterization of CD5+ and CD5– LC subsets.

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Functional characterization of CD5+ and CD5– LC subsets. (A) The percent...
(A) The percentage of CFSElo allogeneic naive CD8+ T cells that were primed for 6–8 days by sorted activated CD5+ and CD5– LCs. Results of 10 independent experiments are shown. Mean ± SD ± SEM CD5+ LCs: 56.4% ± 21.2% ± 6.7%; CD5– LCs: 46.8% ± 20.1% ± 6.3%. (B) Allogeneic CFSE-labeled naive CD8+ T cells primed for 7 days by each LC subset were stained and analyzed by flow cytometry for the expression of granzyme B. The percentage of cells that diluted CFSE and expressed granzyme B is shown. One of 8 experiments is shown. (C) The plot shows the percentage of cells primed by each of the mDC subsets and expressed granzyme B (n = 8). (D) The plots show the expression of IFN-γ and TNF-α by naive CD8+ T cells that were primed by either CD5+ or CD5– LCs. One of 3 experiments is shown. (E) The percentage of CFSElo allogeneic naive CD4+ T cells that were primed for 6–8 days by sorted activated CD5+ or CD5– LCs (n = 9). Mean ± SD ± SEM CD5+ LCs: 71.7% ± 22.3% ± 7.4%; CD5– LCs: 54.5% ± 31.4% ± 10.5%. (F) CFSE-labeled sorted naive CD4+ T cells cultured for 6 days with CD40L-activated CD5+ LCs or CD5– LCs. The plot shows the frequency of IL-22–producing CD4+ T cells that were primed by the different LC subsets (n = 10). Data represent mean ± SEM; *P < 0.05 (A, C, and F), **P < 0.01 (E) by paired Student’s t tests.