Transcript imaging of the development of human T helper cells using oligonucleotide arrays

Lars Rogge, Elisabetta Bianchi, Mauro Biffi, Elisa Bono, S. Y P Chang, Heather Alexander, Chris Santini, Giuliana Ferrari, Luigi Sinigaglia, Monika Seiler, Martin Neeb, Jan Mous, Francesco Sinigaglia, Ulrich Certa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)96-101
Number of pages6
JournalNature Genetics
Volume25
Issue number1
DOIs
Publication statusPublished - May 2000

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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