Jonathan D Crawford, Hong Wang, Daniela Trejo-Zambrano, Raffaello Cimbro, C Conover Talbot, Mekha A Thomas, Ashley M Curran, Alexander A Girgis, John T Schroeder, Andrea Fava, Daniel W Goldman, Michelle Petri, Antony Rosen, Brendan Antiochos, Erika Darrah
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a dramatic sex bias, affecting 9-times more women than men. Activation of toll-like receptor 7 (TLR7) by self-RNA is a central pathogenic process leading to aberrant production of type-I interferon (IFN) in SLE, but the specific RNA molecules that serve as TLR7 ligands have not been defined. We therefore sought to identify female-specific endogenous RNAs containing canonical TLR7 stimulatory motifs. By leveraging gene expression data and the known sequence specificity of TLR7, we identified the female-specific X-inactive specific transcript (XIST) long non-coding RNA as a uniquely rich source of TLR7 ligands in SLE...
September 21, 2023: JCI Insight