Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis.
BACKGROUND
Previous work has identified CD11c(+)CD1c(-) dendritic cells (DCs) as the major "inflammatory" dermal DC population in patients with psoriasis vulgaris and CD1c(+) DCs as the "resident" cutaneous DC population.


OBJECTIVE
We sought to further define molecular differences between these 2 myeloid dermal DC populations.


METHODS
Inflammatory and resident DCs were single-cell sorted from lesional skin biopsy specimens of patients with psoriasis, and the transcriptome of CD11c(+)CD1c(-) versus CD1c(+) DCs was determined. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double-labeled immunofluorescence. Human keratinocytes were cultured for functional studies.


RESULTS
TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors 1 and 2, S100A12/ENRAGE, CD32, and many other inflammatory products were differentially expressed in inflammatory DCs compared with resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c(-) versus CD1c(+) DCs. TRAIL receptors, death receptor 4, and decoy receptor 2 were expressed in keratinocytes and dermal cells. In vitro culture of keratinocytes with TRAIL induced CCL20 chemokine.


CONCLUSIONS
CD11c(+)CD1c(-) inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared with skin-resident CD1c(+) DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis.
Zaba
Lisa C
LC
Laboratory for Investigative Dermatology, the Rockefeller University, New York, NY 10065, USA.
Fuentes-Duculan
Judilyn
J
Eungdamrong
Narat John
NJ
Johnson-Huang
Leanne M
LM
Nograles
Kristine E
KE
White
Traci R
TR
Pierson
Katherine C
KC
Lentini
Tim
T
Suárez-Fariñas
Mayte
M
Lowes
Michelle A
MA
Krueger
James G
JG
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D046228:Microarray Analysis; D011565:Psoriasis / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D015415:Biomarkers; D054418:Chemokine CCL20; D009418:S100 Proteins; C110294:S100A1 protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors
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