Other
23 Authors
- Utz PJ,
- Dou DR,
- Wutz A,
- Chang HY,
- Lundberg EK,
- Kraft K,
- Goldman DW,
- Fiorentino DF,
- Hellström C,
- Srinivasan S,
- Abe BT,
- Yu B,
- Li R,
- Chang S,
- Chung LS,
- Belk JA,
- Chen DC,
- Feng A,
- Shah AA,
- Sjöberg R,
- Casey KM,
- Petri M,
- Zhao Y
| First Author | Dou DR | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 3 | Pages | 733-749.e16 |
| PubMed ID | 38306984 | Mgi Jnum | J:346131 |
| Mgi Id | MGI:7613855 | Doi | 10.1016/j.cell.2023.12.037 |
| Citation | Dou DR, et al. (2024) Xist ribonucleoproteins promote female sex-biased autoimmunity. Cell 187(3):733-749.e16 |
| abstractText | 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 pristane-induced lupus model than wild-type males. Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity. |
