Acknowledging sex differences in immune response is particularly important when we consider the differences between men and women in the incidence of disease. For example, over 80% of autoimmune disease occurs in women, whereas men have a higher incidence of solid tumors compared to women. In general women have stronger innate and adaptive immune responses than men, explaining their ability to clear viral and bacterial infections faster, but also contributing to their increased susceptibility to autoimmune disease. The autoimmune disease systemic lupus erythematosus (SLE) is the archetypical sexually dimorphic disease, with 90% of patients being women. Various mechanisms have been suggested to account for the female prevalence of SLE, including sex hormones, X-linked genes, and epigenetic regulation of gene expression. Here, we will discuss how these mechanisms contribute to pathobiology of SLE and how type I interferons work with them to augment sex specific disease pathogenesis in SLE.
Keywords: IFNα; SLE; X chromosome dosage; epigenetics; estrogen; inflammation; mitochondria; sex disparities.
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