Sex and pubertal differences in the type 1 interferon pathway associate with both X chromosome number and serum sex hormone concentration

Kate Webb, Hannah Peckham, Anna Radziszewska, Madhvi Menon, Paola Oliveri, Fraser Simpson, Claire T. Deakin, Sophie Lee, Coziana Ciurtin, Gary Butler, Lucy R. Wedderburn, Yiannis Ioannou

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.

Original languageEnglish
Article number3167
JournalFrontiers in Immunology
Volume10
Issue numberJAN
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Immunity
  • Interferon
  • Puberty
  • SLE
  • Sex
  • Sex hormone
  • TLR7
  • X Chromosome

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