Transcript imaging of the development of human T helper cells using oligonucleotide arrays.
Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.
Rogge
L
L
Roche Milano Ricerche, Milano, Italy. lars.rogge@roche.com
Bianchi
E
E
Biffi
M
M
Bono
E
E
Chang
S Y
SY
Alexander
H
H
Santini
C
C
Ferrari
G
G
Sinigaglia
L
L
Seiler
M
M
Neeb
M
M
Mous
J
J
Sinigaglia
F
F
Certa
U
U
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases