1 Estradiol Targets T Cell Signaling Pathways in Human Systemic Lupus

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-09, Vol.133 (3), p.428-436
• Main Authors: Walters, Emily, Rider, Virginia, Abdou, Nabih I, Greenwell, Cindy, Svojanovsky, Stan, Smith, Peter, Kimler, Bruce F.
• Format: Article
• Language: English
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.09.002

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.