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

• Published in: Cell reports (Cambridge) Vol. 16; no. 11; pp. 2953 - 2966
• Main Authors: Worah, Kuntal, Mathan, Till S.M., Vu Manh, Thien Phong, Keerthikumar, Shivakumar, Schreibelt, Gerty, Tel, Jurjen, Duiveman-de Boer, Tjitske, Sköld, Annette E., van Spriel, Annemiek B., de Vries, I. Jolanda M., Huynen, Martijn A., Wessels, Hans J., Gloerich, Jolein, Dalod, Marc, Lasonder, Edwin, Figdor, Carl G., Buschow, Sonja I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.09.2016; Cell Press; Elsevier
• Subjects: Biomarkers - metabolism; Caspase 1 - metabolism; Dendritic Cells - metabolism; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunology; Inflammasomes - metabolism; Life Sciences; Medicin och hälsovetenskap; Protein Interaction Maps; Proteomics - methods; Reproducibility of Results; Transcriptome - genetics; RNA-expression; Proteins; Dendritic cells (DCs); Cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.08.023

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. [Display omitted] •We present a comprehensive quantitative proteome comparison of primary human DC subsets•Proteome comparison reveals many expression differences between DC subsets•We provide a resource to derive markers and examine subset functional specialization•pDCs lack caspase-1 and have a decreased inflammasome response Worah et al. present a comprehensive quantitative proteomic comparison of four human blood-derived DC-like subsets. Through integration of proteomic and transcriptomic data, the authors derive expression signatures for each subset that provide a resource for study of subset functional specialization.