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Proteomics of Human Dendritic Cell Subsets Reveals Subset-Specific Surface Markers and Differential Inflammasome Function

Cell Rep. 2016 Sep 13;16(11):2953-2966. doi: 10.1016/j.celrep.2016.08.023.

Abstract

Dendritic cells (DCs) play a key role in orchestrating adaptive immune responses. In human blood, three distinct subsets exist: plasmacytoid DCs (pDCs) and BDCA3+ and CD1c+ myeloid DCs. In addition, a DC-like CD16+ monocyte has been reported. Although RNA-expression profiles have been previously compared, protein expression data may provide a different picture. Here, we exploited label-free quantitative mass spectrometry to compare and identify differences in primary human DC subset proteins. Moreover, we integrated these proteomic data with existing mRNA data to derive robust cell-specific expression signatures with more than 400 differentially expressed proteins between subsets, forming a solid basis for investigation of subset-specific functions. We illustrated this by extracting subset identification markers and by demonstrating that pDCs lack caspase-1 and only express low levels of other inflammasome-related proteins. In accordance, pDCs were incapable of interleukin (IL)-1β secretion in response to ATP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • Caspase 1 / metabolism
  • Dendritic Cells / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Inflammasomes / metabolism*
  • Protein Interaction Maps
  • Proteomics / methods*
  • Reproducibility of Results
  • Transcriptome / genetics

Substances

  • Biomarkers
  • Inflammasomes
  • Caspase 1