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(The FASEB Journal. 2003;17:836-847.)
© 2003 FASEB

Cascades of transcriptional induction during dendritic cell maturation revealed by genome-wide expression analysis

ÖZLEM TÜRECI1, HONGJIN BIAN*, FRANK OLIVER NESTLE{dagger}, LAURA RADDRIZZANI{ddagger}, JAMES A. ROSINSKI*, ANATOLI TASSIS{dagger}, HOLLY HILTON*, MARK WALSTEAD*, UGUR SAHIN2 and JUERGEN HAMMER*,2

III. Department of Internal Medicine, University of Mainz, Germany;
* Genomic and Information Sciences, Hoffmann-La Roche Inc., Nutley, New Jersey, USA;
{dagger} Department of Dermatology, University Hospital Zürich, Switzerland; and
{ddagger} Affymetrix, Santa Clara, California, USA

1Correspondence: III. Medizinische Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Obere Zahlbacherstr. 63, 55131 Mainz, Germany, E-mail: Tureci{at}mail.uni-mainz.de

Dendritic cells (DC) are central regulators of immunity. Signal-induced maturation of DCs is assumed to be the starting point for specific immune responses. To further understand this process, we analyzed the alteration of transcript profiles along the time course of CD40 ligand-induced maturation of human myeloid DCs by Affymetrix GeneChip® microarrays covering >6800 genes. Besides rediscovery of genes already described as associated with DC maturation proving reliability of the methods used, we identified clusterin as novel maturation marker. Looking across the time course, we observed synchronized kinetics of distinct functional groups of molecules whose temporal coregulation underscores known cellular events during dendritic cell maturation. For example, an early-peaking wave of inflammatory chemokines was followed by a sustained increase of constitutive chemokines and accompanied by slow but continuous induction of survival proteins. After an immediate but transient induction of cytokine-responsive transcripts, there was an increased expression of a group of genes involved in not only the regulation of cytokine effects, but also of transcription in general. Our results demonstrate that microarray studies along time courses combined with real-time PCR not only discover new marker molecules with functional implications, but also dissect the molecular kinetics of biological processes identifying complex pathways of regulation.—Türeci, O., Bian, H., Nestle, F. O., Raddrizzani, L., Rosinski, J. A., Tassis, A., Hilton, H., Walstead, M., Sahin, U., Hammer, J. Cascades of transcriptional induction during dendritic cell maturation revealed by genome-wide expression analysis.


Key Words: DC • B cells • apoptotic death




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