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The Journal of Immunology, 2003, 171: 3627-3635.
Copyright © 2003 by The American Association of Immunologists

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes1

Zhi Chen2,*,{dagger}, Riikka Lund*,{ddagger}, Tero Aittokallio§, Minna Kosonen*, Olli Nevalainen§ and Riitta Lahesmaa*

* Turku Centre for Biotechnology, {dagger} Drug Discovery Graduate School, {ddagger} Turku Graduate School of Biomedical Sciences, and § Turku Centre for Computer Science, University of Turku and Åbo Akademi University, Turku, Finland

IL-4, primarily produced by T cells, mast cells, and basophiles, is a cytokine which has pleiotropic effects on the immune system. IL-4 induces T cells to differentiate to Th2 cells and activated B lymphocytes to proliferate and to synthesize IgE and IgG1. IL-4 is particularly important for the development and perpetuation of asthma and allergy. Stat6 is the protein activated by signal transduction through the IL-4R, and studies with knockout mice demonstrate that Stat6 is critical for a number of IL-4-mediated functions including Th2 development and production of IgE. In the present study, novel IL-4- and Stat6-regulated genes were discovered by using Stat6-/- mice and Affymetrix oligonucleotide arrays. Genes regulated by IL-4 were identified by comparing the gene expression profile of the wild-type T cells induced to polarize to the Th2 direction (CD3/CD28 activation + IL-4) to gene expression profile of the cells induced to proliferate (CD3/CD28 activation alone). Stat6-regulated genes were identified by comparing the cells isolated from the wild-type and Stat6-/- mice; in this experiment the cells were induced to differentiate to the Th2 direction (CD3/CD28 activation + IL-4). Our study demonstrates that a number a novel genes are regulated by IL-4 through Stat6-dependent and -independent pathways. Moreover, elucidation of kinetics of gene expression at early stages of cell differentiation reveals several genes regulated rapidly during the process, suggesting their importance for the differentiation process.




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