Diana R Dou, Yanding Zhao, Julia A Belk, Yang Zhao, Kerriann M Casey, Derek C Chen, Rui Li, Bingfei Yu, Suhas Srinivasan, Brian T Abe, Katerina Kraft, Ceke Hellström, Ronald Sjöberg, Sarah Chang, Allan Feng, Daniel W Goldman, Ami A Shah, Michelle Petri, Lorinda S Chung, David F Fiorentino, Emma K Lundberg, Anton Wutz, Paul J Utz, Howard Y Chang
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...
February 1, 2024: Cell