TY - JOUR
T1 - A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease
AU - Korenfeld, Daniel
AU - Gorvel, Laurent
AU - Munk, Adiel
AU - Man, Joshua
AU - Schaffer, Andras
AU - Tung, Thomas
AU - Mann, Caroline
AU - Klechevsky, Eynav
N1 - Funding Information:
We thank Erica Maria Lantelme, Marina Cella, Dorjan Brinja, and Emily Mannin at the Washington University School of Medicine in St. Louis Department of Pathology and Immunology for their help; Lisa Wu for help with editing this manuscript; and Kang Liu for providing the MS-5 cell line. We thank the surgeons, nurses, and staff at Barnes-Jewish Hospital and the Washington University School of Medicine in St. Louis Department of Surgery for providing access to skin samples. We thank Paul Allen, Gwendalyn Randolph, and Andrey Shaw for their advice and critical reading of the manuscript. This work was supported by funding from the Washington University School of Medicine in St. Louis Department of Pathology and Immunology and the Siteman Cancer Center to EK. This work was presented at the CIML 40th anniversary conference in Marseille, France, in September 2016; at the Aegean International Conference on Human & Translational Immunology in Rhodes, Greece, in September 2016 (51); at the 14th International Symposium on Dendritic Cells in Shanghai, China, in October 2016; and at the Inflammatory Skin Disease Summit — The Translational Revolution, The New York Academy of Medicine, in New York, New York, USA, in November 2016.
Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/9/21
Y1 - 2017/9/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85039052152&partnerID=8YFLogxK
U2 - 10.1172/JCI.INSIGHT.96101
DO - 10.1172/JCI.INSIGHT.96101
M3 - Article
C2 - 28931765
AN - SCOPUS:85039052152
VL - 2
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 18
M1 - :e96101
ER -