Patients with systemic lupus erythematosus have autoantibodies that recognize RNA-binding proteins and have type I interferon signatures. In Science, Behrens and colleagues show that Ro60, a known lupus autoantigen, forms complexes with RNAs expressed from Alu element–expressing endogenous retroviruses. Patients with lupus have higher concentrations of Ro60-Alu–containing RNA in their serum than do healthy control subjects. Ro60 recognizes a 3′ untranslated region in Alu RNA. Knockdown of Ro60 in human B cell lines increases the abundance of Alu RNA, which suggests that Ro60 acts to limit the availability of Alu RNA to endogenous RNA sensors. A feed-forward inflammatory loop seems to exist, as type I interferon drives Alu expression, which in turn activates TLR7 signaling to increase interferon expression. The authors speculate that this Alu-recognition pathway served as an evolutionary advantage to enhance inflammatory antiviral responses but results in heightened autoimmunity.
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Dempsey, L. SLE links to Alu elements. Nat Immunol 16, 1113 (2015). https://doi.org/10.1038/ni.3301
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DOI: https://doi.org/10.1038/ni.3301