Estrogen-dependent upregulation of IRF5 in human immune cells

• Objective: To contribute to the knowledge of the mechanisms behind the strong sex-biased prevalence of SLE, we investigated the role of estrogen on the expression of one of the strongest associated gene with SLE, the interferon regulatory factor 5 (IRF5), in human immune cells. Material and methods:  IRF5, as well as IRF3, IRF4, IRF7 and IRF9 expression was measured in PBMCs, LCLs, monocytes and macrophages from both male and female origin. Cells were treated with different concentrations of estrogen and gene expression was measured by quantitative RT-PCR. Results: We found that the initial levels of IRF5 in PBMC were almost 2-fold higher in women than men, although not reaching statistical significance. After 12 h in culture the IRF5 levels became roughly equal in both sexes, and further stimulation with estrogen lead to up-regulation of IRF5 expression in both PBMCs and monocytes in both women and men. No difference was seen for IRF3, IRF4, IRF7 and IRF9 expression, and no gene was up-regulated in LCLs, upon estrogen treatment, regardless of the gender. Conclusions: We showed that in human PBMCs and monocytes from healthy individuals IRF5 expression can be regulated by exogenous estrogen. This feature might be specific to IRF5 since four other IRF genes tested did not show any up-regulation in these cells.

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