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Is sex bias orchestrated in the skin?

Nature Immunology volume 18, pages 142–143 (2017)Cite this article

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The identification of VGLL3 as a transcription (co-)factor that underlies the sex bias of the human immune system further underscores the relevance of research into this area.

Autoimmune diseases affect around 8% of the population, with a clear sex bias toward women (∼78% overall, and up to 95% for specific diseases)1. The molecular pathways underlying this bias, however, have remained unclear. In this issue of Nature Immunology, Liang et al. study the skin transcriptome of healthy men and women for sex-specific molecular signatures and identify VGLL3 as a sex-specific transcription (co-)factor in the skin2. Integration of transcriptomics data, data obtained by knockdown VGLL3 and the genetic risk variants from literature has further shown that VGLL3 regulates several genes encoding products previously demonstrated to be associated with autoimmune diseases, including the cytokine BAFF, the integrin αM, complement component C3, and interleukin 7 (IL-7) and its receptor IL-7R, and thereby contributes to the female bias in the prevalence of these conditions.

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Figure 1: Complex regulation of the immune response underlies sex bias in the risk of infection and autoimmune diseases.

Marina Corral Spence/Springer Nature

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Authors and Affiliations

  1. Aridaman Pandit and Timothy R.D.J. Radstake are in the Department of Rheumatology & Clinical Immunology, Laboratory of Translational Immunology, Utrecht University Medical Center, Utrecht, the Netherlands.,

    Aridaman Pandit & Timothy R D J Radstake

  2. Linde Meyaard is in the Laboratory of Translational Immunology, Utrecht University Medical Center, Utrecht, the Netherlands.,

    Linde Meyaard

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  1. Aridaman Pandit
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  2. Linde Meyaard
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  3. Timothy R D J Radstake
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Correspondence to Timothy R D J Radstake.

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Pandit, A., Meyaard, L. & Radstake, T. Is sex bias orchestrated in the skin?. Nat Immunol 18, 142–143 (2017). https://doi.org/10.1038/ni.3658

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