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

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. and Buschow, Sonja I. (2016) Proteomics of Human Dendritic Cell Subsets Reveals Subset-Specific Surface Markers and Differential Inflammasome Function. Cell Reports, 16 (11). pp. 2953-2966. ISSN 2211-1247

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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.

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