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Expression analysis and functional activity of interleukin-7 splice variants

Genes & Immunity volume 10, pages 132–140 (2009)Cite this article

Abstract

Alternative splicing results in multiple protein isoforms derived from a single gene. The magnitude of this process ranges from a complete loss of function to gain of new function. We examined, as a paradigm, alternative splicing of the non-redundant human cytokine, interleukin-7 (IL-7). We show that extensive IL-7 splicing in human tissues of different histology, including MTB+ granuloma lesions, transformed tissue and tumor cell lines. IL-7 splice variants were expressed as recombinant proteins. A differentially spliced IL-7 isoform, lacking exon 5, leads to STAT-5 phosphorylation in CD4+ and CD8+ T cells, promotes thymocyte maturation and T-cell survival. Human tumor lesions show aberrant IL-7 isoform expression, as compared with the autologous, non-transformed tissue. Alternatively spliced cytokines, such as IL-7, represent candidates for diagnostics and therapeutic interventions.

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Acknowledgements

We thank Wolfgang Walter for screening cDNA for IL-7 transcripts and cloning, Professor Markus Heinemann, Department of Pediatric Cardiac Surgery, University of Mainz for provision of human thymic tissues, Professor E Jäger, Ludwig Institute for Cancer Research, Frankfurt, Germany for freshly harvested human tumor tissue and Professor H Pilch, Department of Gynecology, Mainz for analysis of tissue sections from patients with cervical cancer. Yen Ngo, MEB, Karolinska Institutet, Stockholm, Sweden for statistical analysis and Dr Sharon Kühlmann-Berenzon, SMI, Stockholm, Sweden for statistical advice. We are indebted to Professor Stoerkel and Dr Atkins, University of Wuppertal, Germany, for performing microdissection of thymic tissues. The study was supported by Karolinska Institutet and from a grant to MM from Cancerfonden, Sweden.

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Authors and Affiliations

  1. Microbiology, Tumor and Cell Biology Center (MTC) and SMI, Nobels Väg 18, Karolinska Institutet, Stockholm, Sweden

    N K Vudattu, I Magalhaes & M J Maeurer

  2. Department of Medical Microbiology, University of Mainz, Hochhaus Augustusplatz, Mainz, Germany

    H Hoehn & D Pan

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  1. N K Vudattu
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Correspondence to M J Maeurer.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Vudattu, N., Magalhaes, I., Hoehn, H. et al. Expression analysis and functional activity of interleukin-7 splice variants. Genes Immun 10, 132–140 (2009). https://doi.org/10.1038/gene.2008.90

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