PMID- 20881193 OWN - NLM STAT- MEDLINE DCOM- 20101112 LR - 20101021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 185 IP - 9 DP - 2010 Nov 1 TI - TGF-beta1 accelerates dendritic cell differentiation from common dendritic cell progenitors and directs subset specification toward conventional dendritic cells. PG - 5326-35 LID - 10.4049/jimmunol.0903950 [doi] AB - Dendritic cells (DCs) in lymphoid tissue comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs) that develop from common DC progenitors (CDPs). CDPs are Flt3(+)c-kit(int)M-CSFR(+) and reside in bone marrow. In this study, we describe a two-step culture system that recapitulates DC development from c-kit(hi)Flt3(-/lo) multipotent progenitors (MPPs) into CDPs and further into cDC and pDC subsets. MPPs and CDPs are amplified in vitro with Flt3 ligand, stem cell factor, hyper-IL-6, and insulin-like growth factor-1. The four-factor mixture readily induces self-renewal of MPPs and their progression into CDPs and has no self-renewal activity on CDPs. The amplified CDPs respond to all known DC poietins and generate all lymphoid tissue DCs in vivo and in vitro. Additionally, in vitro CDPs recapitulate the cell surface marker and gene expression profile of in vivo CDPs and possess a DC-primed transcription profile. TGF-beta1 impacts on CDPs and directs their differentiation toward cDCs. Genome-wide gene expression profiling of TGF-beta1-induced genes identified instructive transcription factors for cDC subset specification, such as IFN regulatory factor-4 and RelB. TGF-beta1 also induced the transcription factor inhibitor of differentiation/DNA binding 2 that suppresses pDC development. Thus, TGF-beta1 directs CDP differentiation into cDCs by inducing both cDC instructive factors and pDC inhibitory factors. FAU - Felker, Piritta AU - Felker P AD - Department of Cell Biology, Medical Faculty, Rheinisch-Westfalische Technische Hochschule, Aachen, Germany. FAU - Sere, Kristin AU - Sere K FAU - Lin, Qiong AU - Lin Q FAU - Becker, Christiane AU - Becker C FAU - Hristov, Mihail AU - Hristov M FAU - Hieronymus, Thomas AU - Hieronymus T FAU - Zenke, Martin AU - Zenke M LA - eng SI - GEO/GSE22432 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100929 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Animals MH - Cell Differentiation/*immunology MH - Cell Separation MH - Dendritic Cells/*cytology/immunology/metabolism MH - Flow Cytometry MH - Gene Expression MH - Gene Expression Profiling MH - Gene Knock-In Techniques MH - Hematopoietic Stem Cells/*cytology/immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Multipotent Stem Cells/cytology/immunology/metabolism MH - Oligonucleotide Array Sequence Analysis MH - Transforming Growth Factor beta1/*immunology/metabolism EDAT- 2010/10/01 06:00 MHDA- 2010/11/13 06:00 CRDT- 2010/10/01 06:00 PHST- 2010/10/01 06:00 [entrez] PHST- 2010/10/01 06:00 [pubmed] PHST- 2010/11/13 06:00 [medline] AID - jimmunol.0903950 [pii] AID - 10.4049/jimmunol.0903950 [doi] PST - ppublish SO - J Immunol. 2010 Nov 1;185(9):5326-35. doi: 10.4049/jimmunol.0903950. Epub 2010 Sep 29.