Cascades of transcriptional induction during dendritic cell maturation revealed by genome-wide expression analysis.
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
Ozlem
O
III. Department of Internal Medicine, University of Mainz, Germany. Tureci@mail.uni-mainz.de
Bian
Hongjin
H
Nestle
Frank Oliver
FO
Raddrizzani
Laura
L
Rosinski
James A
JA
Tassis
Anatoli
A
Hilton
Holly
H
Walstead
Mark
M
Sahin
Ugur
U
Hammer
Juergen
J
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014158:Transcription, Genetic; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D012313:RNA; D000097802:CD83 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse