Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration
Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration
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DOI：
10.3389/fimmu.2018.03167
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发表时间：
2019-01-15
影响因子：
7.3
通讯作者：
Ioannou, Yiannis
中科院分区：
文献类型：
--
作者：
Webb, Kate;Peckham, Hannah;Ioannou, Yiannis
1型干扰素（IFN）是一种抗病毒细胞因子家族，在青少年发病的系统性红斑狼疮（jSLE）中很重要，jSLE在青春期前后的女性中更常见。我们报告说，浆细胞样树突状细胞（pDC）从健康女性产生更多的1型干扰素后，Toll样受体（TLR）7信号比男性，甚至在青春期前，但青春期本身与1型干扰素的生产增加。一个独特的人类模型使我们能够证明这与X染色体数目和血清睾酮浓度有关，其方式取决于存在的X染色体数目。此外，我们已经表明，pDC在女性中总体上更活化，并且青春期后女性中免疫细胞TLR7基因表达更高。因此，性激素和X染色体数目与1型IFN反应单独和交互相关，这有助于我们理解为什么女性更容易在青春期后发生IFN介导的疾病，如jSLE。
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.