1 Estradiol Targets T Cell Signaling Pathways in Human Systemic Lupus

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/− estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-α signaling. Measurement of interferon-α pathway target gene expression revealed significant differences (p = 0.043) in DRIP150 (+/− estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r = 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.