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A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells

Genes & Immunity volume 13, pages 346–350 (2012)Cite this article

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Abstract

T helper (Th)17 cells constitute a distinct subset of CD4+ helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)γt directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel RORγt isoform, RORγt-Δ(5–8), which lacks the hinge-encoding exons 5–8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that RORγt-Δ(5–8) acts as a dominant-negative regulator of RORγt-mediated gene regulation and the balance between the full-length RORγt and the novel repressor isoform may arbitrate IL-17 production in human T cells.

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Acknowledgements

This study was supported by National Institute of Health Grants R01 AI85567 and R01 AI49954 (to GCT) and the Deutsche Forschungsgemeinschaft (grant RA1927/1-1 to TR). We thank Melissa Zajdel for technical assistance.

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Author notes

  1. T Rauen and Y-T Juang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    T Rauen, Y-T Juang, C M Hedrich, K Kis-Toth & G C Tsokos

  2. Department of Nephrology and Clinical Immunology, RWTH University of Aachen, Aachen, Germany

    T Rauen

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  1. T Rauen
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  2. Y-T Juang
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Correspondence to G C Tsokos.

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Rauen, T., Juang, YT., Hedrich, C. et al. A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells. Genes Immun 13, 346–350 (2012). https://doi.org/10.1038/gene.2011.85

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