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Identification of alternatively spliced Il7r transcripts in mouse T cells that encode soluble IL-7Rα

Cellular & Molecular Immunology volume 17, pages 1284–1286 (2020)Cite this article

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All lymphocytes depend on the cytokine IL-7 for their development and homeostasis, and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably, the IL-7 receptor α-chain (IL-7Rα) does not only exist as a membrane-bound form but is also found as a soluble protein in human serum.2,3 The exact role of soluble IL-7Rα (sIL-7Rα) proteins remains to be determined. However, increased amounts of sIL-7Rα have been associated with an increased risk of inflammation and autoimmunity.3,4 Mechanistically, sIL-7Rα proteins can be generated by alternative splicing of Il7r gene transcripts that encode IL-7Rα. Curiously, however, such Il7r splice isoforms have only been described in humans and have never been described in mice.5 Consequently, the importance of Il7r alternative splice products that are not conserved across species has remained questionable. Here, we report the unexpected identification of an alternatively spliced Il7r transcript in mouse T cells that is distinct in its splice mechanism compared to that of human splice isoforms, but that could potentially produce soluble IL-7Rα proteins. Thus, the generation of IL-7Rα mRNA splice isoforms is a mechanism that is conserved between humans and mice. Assessing its physiological significance will lead to new insights into T cell immunology.

Using RT-PCR primers that flank either the human or mouse Il7r exon 6, we confirmed the generation of alternatively spliced IL-7Rα pre-mRNA transcripts (Il7r-Δexon 6) exclusively in human T cells (Fig. 1a, b and Supplementary Materials). The 200-bp Il7r-Δexon 6 splice isoform was also found in PBMCs of monkeys and pigs, but it was conspicuously absent in mice (Fig. 1b, c). Curiously, however, we found that mouse T cells expressed a novel 400-bp PCR product that was not present in pig, monkey, or human cells (Fig. 1b, c). Molecular cloning and DNA sequencing identified this PCR product as a novel Il7r splice variant that was specific to mice and contained exon 6 and a part of intron 5 (Fig. 1a, d). Consequently, the RT-PCR products amplified by primers1* and -2* resulted in two distinct bands; the 300-bp product represents the conventional membrane form of IL-7Rα, while the larger 400-bp product corresponds to a novel splice isoform that is only found in mouse immune cells (Fig. 1b). Because the newly identified splice product contains a part of intron 5 (Fig. 1d), we refer to this isoform as “Il7r-intron 5+”.

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Acknowledgements

This work was supported by the Intramural Research Program of the US National Institutes of Health, the National Cancer Institute, the Center for Cancer Research, and the Financial Support Project, Long-Term Overseas Dispatch, Tenure-Track Faculty, Pusan National University.

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  1. These authors contributed equally: Hee Yeun Won, Yuna Jo

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  1. Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Hee Yeun Won & Jung-Hyun Park

  2. Department of Anatomy, Pusan National University School of Medicine, Yangsan, 50612, South Korea

    Yuna Jo, Ju A Shim & Changwan Hong

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  1. Hee Yeun Won
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H.Y.W., Y.J., J.A.S., and C.H. performed experiments, analyzed data, and generated figures. C.H. and J.H.P. directed the study and wrote the paper.

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Correspondence to Changwan Hong or Jung-Hyun Park.

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Won, H.Y., Jo, Y., Shim, J.A. et al. Identification of alternatively spliced Il7r transcripts in mouse T cells that encode soluble IL-7Rα. Cell Mol Immunol 17, 1284–1286 (2020). https://doi.org/10.1038/s41423-020-0409-8

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