Coexpression of the Interleukin-13 and Interleukin-4 Genes Correlates With Their Physical Linkage in the Cytokine Gene Cluster on Human Chromosome 5q23-31

• Published in: Blood 1996-04, Vol.87 (8), p.3316-3326
• Main Authors: Dolganov, Gregory, Bort, Susan, Lovett, Michael, Burr, John, Schubert, Lisa, Short, Douglas, McGurn, Mary, Gibson, Christine, Lewis, David B.
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Analysis of the immune response. Humoral and cellular immunity; Base Sequence; Biological and medical sciences; Chromosomes, Human, Pair 5 - genetics; Cyclosporine - pharmacology; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; Genetic Linkage; Humans; Immunobiology; Interleukin-13 - biosynthesis; Interleukin-13 - genetics; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Lymphocyte Activation - drug effects; Lymphokines, interleukins ( function, expression); Mitogens - pharmacology; Molecular Sequence Data; NFATC Transcription Factors; Nuclear Proteins; Promoter Regions, Genetic - genetics; Regulatory factors and their cellular receptors; Regulatory Sequences, Nucleic Acid; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Transcription Factors - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.8.3316.bloodjournal8783316

Interleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5. To investigate the regulation of IL-13 gene expression by T cells, we isolated and sequenced the human IL-13 gene, analyzed its 5-flanking region for potential transcriptional activation elements, and examined its expression in nontransformed T-lineage cell populations. The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island. The IL-13 gene 5’ flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells. Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation. Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein, nuclear factor-activated T cells, preformed (NF-ATp), when incubated with nuclear protein extracts from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro, indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells contain higher levels of nuclear NF-ATp, capable of binding to P elements of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes.