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Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis

2010; Elsevier BV; Volume: 125; Issue: 6 Linguagem: Inglês

10.1016/j.jaci.2010.03.018

1097-6825

Lisa C. Zaba, Judilyn Fuentes‐Duculan, Narat J. Eungdamrong, Leanne M. Johnson-Huang, Kristine Nograles, Traci R. White, Katherine C. Pierson, Tim Lentini, Mayte Suárez‐Fariñas, Michelle A. Lowes, James G. Krueger,

Cytokine Signaling Pathways and Interactions

BackgroundPrevious 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.ObjectiveWe sought to further define molecular differences between these 2 myeloid dermal DC populations.MethodsInflammatory 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.ResultsTNF-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.ConclusionsCD11c+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.