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IL7RA genetic variants differentially affect IL-7Rα expression and alternative splicing: a role in autoimmune and infectious diseases?

Genes & Immunity volume 21, pages 83–90 (2020)Cite this article

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Abstract

Interleukin-7 receptor α chain (IL-7Rα) single nucleotide polymorphisms (SNPs) are associated with susceptibility to immunopathologies like autoimmune and inflammatory diseases. The current hypothesis about underlying mechanisms is based on the regulation of IL-7 availability for self-reactive T cells by influencing the generation of a soluble (s)IL-7Rα variant. This assumption was mainly predicated on the well-defined IL7RA SNP rs6897932, which affects alternative splicing and causes aberrant generation of the sIL-7Rα variant with potential effects on the IL-7 serum reservoir. However, more recent studies shed light on novel functions of autoimmunity risk-associated IL7RA SNPs and characterized the largely neglected effect of rs6897932 on membrane (m)IL-7Rα expression. These findings as well as a described role of impaired mIL-7Rα expression and IL7RA SNP influence on chronic infectious diseases necessitates the reevaluation of previous findings on the role of IL7RA SNPs in immunopathology.

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Fig. 1: IL-7Rα exon composition, cellular localization, and exonic SNPs are schematically shown.

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Acknowledgements

MJ was supported by the German Research Foundation (DFG, JA 1479/5-1; DFG, JA 1479/9-1). JS was supported by a grant from the Elterninitiative Kinderkrebsklinik eV.

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  1. These authors contributed equally: Christian Lundtoft, Julia Seyfarth

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  1. Department of General Pediatrics, Neonatology, and Pediatric Cardiology, Medical Faculty, University Children’s Hospital, Moorenstr. 5, 40225, Duesseldorf, Germany

    Christian Lundtoft, Julia Seyfarth & Marc Jacobsen

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Lundtoft, C., Seyfarth, J. & Jacobsen, M. IL7RA genetic variants differentially affect IL-7Rα expression and alternative splicing: a role in autoimmune and infectious diseases?. Genes Immun 21, 83–90 (2020). https://doi.org/10.1038/s41435-019-0091-y

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