title: Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis.
abstract: 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.
authors.affiliation: Laboratory for Investigative Dermatology, the Rockefeller University, New York, NY 10065, USA.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Zaba
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Narat John
authors.initials: NJ
authors.lastname: Eungdamrong
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Johnson-Huang
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Nograles
authors.forename: Traci R
authors.initials: TR
authors.lastname: White
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Pierson
authors.forename: Tim
authors.initials: T
authors.lastname: Lentini
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: 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
chemical_list: 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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