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Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells

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Abstract

Interleukin 23 (IL-23) is a new member of the IL-12 family that plays a critical role in promoting the proliferation of memory T helper 1 cells. The heterodimerized IL-23 receptor is composed of a shared IL-12 receptor beta 1 (IL-12Rβ1) and an IL-12Rβ2-related molecule called IL-23R. The standard form of IL-23R is encoded by at least 12 exons. Here, we demonstrate that at least six spliced isoforms of IL-23R (IL-23R1 to 6) can be generated through alternative splicing. The splicing strategies for the IL-23R gene are complicated and most often result in the deletion of exon 7 and/or exon 10. Translation prediction revealed that these spliced variants result in either premature termination to give rise to a diverse form of receptor ectodomain, or a frameshift to generate various lengths of the IL-23R endodomain. Differential expressions of IL-23R spliced variants are observed in natural killer and CD3+CD4+ T cells. The expressions of these spliced variants are also prevalently and complicatedly regulated in tumor cell lines. Interestingly, only IL-23R2 and/or IL-23R4 variants are predominantly detected in certain human lung carcinomas, but not in their resected normal margin tissues. Thus, our results indicate that the regulation of alternative splicing on the IL-23R gene is complicated, and the preferential expression of certain IL-23R spliced variants may be a contributive factor to the pathogenesis of certain cancers.

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Acknowledgements

The authors would like to thank Dr. Liang-Hu Qu for critical comments on the manuscript. This work was supported by grants from National Natural Science Foundation (30070039, 30370324, and 30230200) and Beijing Natural Science Foundation (7032035).

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Authors and Affiliations

  1. Department of Microbiology and Etiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China

    Xiang-Yue Zhang, Hai-Jing Zhang, Yun Zhang, Ying-Jie Fu, Shu-Hui Wang & Li Liu

  2. Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005, China

    Li-Ping Zhu

  3. Department of Radiation Oncology (Chest Section), Cancer Institute (Hospital), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China

    Jie He

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  1. Xiang-Yue Zhang
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Correspondence to Li Liu.

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Zhang, XY., Zhang, HJ., Zhang, Y. et al. Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells. Immunogenetics 57, 934–943 (2006). https://doi.org/10.1007/s00251-005-0067-0

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