17β-estradiol and B-cell intrinsic type I interferon amplify toll-like receptor 7 signaling loop in B cells of female lupus prone BXD2 mice

Abstract While systemic lupus erythematosus (SLE) disproportionally affects women versus men, elevation in 17β -estradiol (E2) alone is not sufficient to promote the development of autoantibody producing B cells. The objective present study determine if B-cell intrinsic mechanisms contribute increased TLR7 response E2 stimulation. We identified that there were elevated circulating levels young African American (AA) SLE patients (24–41 yr-old), compared older AA (42–56 yr-old) and European (24–66 yr-old). Circulating positively correlated with anti-Smith (Sm) expression interferon-beta (IFNβ) naïve cells (n=39). Mouse studies used stimulates IFNβ sex plays a role influence cell responses E2. Serum Sm/RNP RNP autoantibodies female prone BXD2 mice post-puberty (12-wk-old) but pre-puberty (4–6-wk-old). At stage (>12 wk-old), significantly anti-DNA anti-Sm mice, male mice. This was associated an TLR7-induced CD69 transitional 1 (T1: CD23 −IgM +CD93 +) Interestingly, stimulation promoted intracellular T1 from Together, our results suggest combination susceptibility induction may play individuals predisposed SLE. supported by grants VA Merit Review grant (I01BX004049), NIH R01-AI-071110, R01 AI134023, Lupus Research Alliance Distinguished Innovator Award J.D.M, LRA Target Identification H-C.H., P30-AR-048311