Transcriptional Profiling of Human Dendritic Cell Populations and Models - Unique Profiles of In Vitro Dendritic Cells and Implications on Functionality and Applicability

Background: Dendritic cells (DCs) comprise heterogeneous populations of cells, which act as central orchestrators of the immune response. Applicability of primary DCs is restricted due to their scarcity and therefore DC models are commonly employed in DC-based immunotherapy strategies and in vitro tests assessing DC function. However, the interrelationship between the individual in vitro DC models and their relative resemblance to specific primary DC populations remain elusive. Objective: To describe and assess functionality and applicability of the available in vitro DC models by using a genome-wide transcriptional approach. Methods: Transcriptional profiling was performed with four commonly used in vitro DC models (MUTZ-3-DCs, monocyte-derived DCs, CD34-derived DCs and Langerhans cells (LCs)) and nine primary DC populations (dermal DCs, LCs, blood and tonsillar CD123(+), CD1c(+) and CD141(+) DCs, and blood CD16(+) DCs). Results: Principal Component Analysis showed that transcriptional profiles of each in vitro DC model most closely resembled CD1c(+) and CD141(+) tonsillar myeloid DCs (mDCs) among primary DC populations. Thus, additional differentiation factors may be required to generate model DCs that more closely resemble other primary DC populations. Also, no model DC stood out in terms of primary DC resemblance. Nevertheless, hierarchical clustering showed clusters of differentially expressed genes among individual DC models as well as primary DC populations. Furthermore, model DCs were shown to differentially express immunologically relevant transcripts and transcriptional signatures identified for each model DC included several immune-associated transcripts. Conclusion: The unique transcriptional profiles of in vitro DC models suggest distinct functionality in immune applications. The presented results will aid in the selection of an appropriate DC model for in vitro assays and assist development of DC-based immunotherapy.