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

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

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
2
Centre d'Immunologie, de Marseille-Luminy, Aix Marseille University UM2, Inserm, U1104, CNRS UMR7280, Cedex 09, 13288 Marseille, France.
3
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
4
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet, 171 76 Stockholm, Sweden.
5
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; Department of Medical Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
6
Radboud Proteomics Centre, Department of Laboratory Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
7
Radboud Proteomics Centre, Department of Laboratory Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
8
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; School of Biomedical and Healthcare Sciences, B427 Portland Square, Plymouth University, Drake Circus, Plymouth, Devon PL4 8AA, UK.
9
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Electronic address: carl.figdor@radboudumc.nl.
10
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CN Rotterdam, the Netherlands. Electronic address: s.buschow@erasmusmc.nl.

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.

PMID:
27626665
PMCID:
PMC5039226
DOI:
10.1016/j.celrep.2016.08.023
[Indexed for MEDLINE]
Free PMC Article

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