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

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

Research output: Contribution to journalArticle

74 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1261-1268.e9
JournalJournal of Allergy and Clinical Immunology
Volume125
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • CCL20
  • CD32
  • S100A12
  • TRAIL
  • Toll-like receptor 1
  • Toll-like receptor 2
  • dendritic cell
  • inflammation
  • psoriasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zaba, L. C., Fuentes-Duculan, J., Eungdamrong, N. J., Johnson-Huang, L. M., Nograles, K. E., White, T. R., Pierson, K. C., Lentini, T., Suárez-Fariñas, M., Lowes, M. A., & Krueger, J. G. (2010). Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis. Journal of Allergy and Clinical Immunology, 125(6), 1261-1268.e9. https://doi.org/10.1016/j.jaci.2010.03.018