Xist ribonucleoproteins promote female sex-biased autoimmunity

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multi-organ pathology in a…

• HH
  Howard Hughes Medical Institute
• SR
  Scleroderma Research Foundation
• M
  Medpace
• JH
  Johns Hopkins University
• KC
  Kao Corporation
• NI
  National Institutes of Health
• NI
  National Institute of Arthritis and Musculoskeletal and Skin Diseases

  Awards: AR069572, T32 AR007422, K99/R00, T32 AR050942, R01-AR069572