Figure 1.

Sex differences in systemic lupus erythematosus (SLE). Numerous mechanisms have been demonstrated to contribute to the sex-dependent development of SLE in both patients and animal models. Sex hormones and receptors, sex chromosomes, and Toll-like receptors all have been implicated as key mechanisms in SLE. In female patients and mice (left), elevated estrogen and estrogen receptor signaling, along with the X chromosome-linked proinflammatory genes (Cxcr3, Cd40, Tlr7), contribute to the frequency and/or severity of SLE. In male patients and mice (right), an imbalance of estrogen and testosterone, elevated estrogen receptor signaling, increased copies of the X chromosome (Klinefelter’s syndrome), and TLR7 signaling contribute to the severity and development of SLE.