Proteomics of Human Dendritic Cell Subsets Reveals Subset-Specific Surface Markers and Differential Inflammasome Function.
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.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Kuntal
K
Worah
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Till S M
TSM
Mathan
Centre d'Immunologie, de Marseille-Luminy, Aix Marseille University UM2, Inserm, U1104, CNRS UMR7280, Cedex 09, 13288 Marseille, France.
Thien Phong
TP
Vu Manh
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Shivakumar
S
Keerthikumar
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Gerty
G
Schreibelt
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Jurjen
J
Tel
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Tjitske
T
Duiveman-de Boer
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.
Annette E
AE
Sköld
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Annemiek B
AB
van Spriel
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.
I Jolanda M
IJM
de Vries
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Martijn A
MA
Huynen
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.
Hans J
HJ
Wessels
Radboud Proteomics Centre, Department of Laboratory Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Jolein
J
Gloerich
Centre d'Immunologie, de Marseille-Luminy, Aix Marseille University UM2, Inserm, U1104, CNRS UMR7280, Cedex 09, 13288 Marseille, France.
Marc
M
Dalod
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.
Edwin
E
Lasonder
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.
Carl G
CG
Figdor
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.
Sonja I
SI
Buschow
D015415:Biomarkers / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics
D015415:Biomarkers; D058847:Inflammasomes; D020170:Caspase 1