PMID- 23341914 OWN - NLM STAT- MEDLINE DCOM- 20130709 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - Transcriptional profiling of human dendritic cell populations and models--unique profiles of in vitro dendritic cells and implications on functionality and applicability. PG - e52875 LID - 10.1371/journal.pone.0052875 [doi] LID - e52875 AB - 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. FAU - Lundberg, Kristina AU - Lundberg K AD - Department of Immunotechnology, Lund University, Lund, Sweden. kristina.lundberg@immun.lth.se FAU - Albrekt, Ann-Sofie AU - Albrekt AS FAU - Nelissen, Inge AU - Nelissen I FAU - Santegoets, Saskia AU - Santegoets S FAU - de Gruijl, Tanja D AU - de Gruijl TD FAU - Gibbs, Sue AU - Gibbs S FAU - Lindstedt, Malin AU - Lindstedt M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130114 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (RNA, Messenger) SB - IM MH - Cluster Analysis MH - Dendritic Cells/*cytology/*immunology MH - *Gene Expression Profiling MH - Gene Expression Regulation MH - Humans MH - Immune System Diseases/therapy MH - Immunologic Tests MH - *Models, Immunological MH - Palatine Tonsil/cytology MH - Phenotype MH - RNA, Messenger/genetics/metabolism MH - Skin/cytology PMC - PMC3544800 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/01/24 06:00 MHDA- 2013/07/10 06:00 PMCR- 2013/01/14 CRDT- 2013/01/24 06:00 PHST- 2012/09/04 00:00 [received] PHST- 2012/11/22 00:00 [accepted] PHST- 2013/01/24 06:00 [entrez] PHST- 2013/01/24 06:00 [pubmed] PHST- 2013/07/10 06:00 [medline] PHST- 2013/01/14 00:00 [pmc-release] AID - PONE-D-12-26955 [pii] AID - 10.1371/journal.pone.0052875 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e52875. doi: 10.1371/journal.pone.0052875. Epub 2013 Jan 14.