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  • Dou, Diana R.Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)

Xist ribonucleoproteins promote female sex-biased autoimmunity

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Elsevier BV,2024
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-343195
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-343195URI
  • https://doi.org/10.1016/j.cell.2023.12.037DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20240209
  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Zhao, YandingCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Belk, Julia A.Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Zhao, YangCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Casey, Kerriann M.Department of Comparative Medicine, Stanford University, Stanford, CA, USA (author)
  • Chen, Derek C.Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Li, RuiCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Yu, BingfeiCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Srinivasan, SuhasCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Abe, Brian T.Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Kraft, KaterinaCenter for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Hellström, CeciliaKTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1doy1fn (author)
  • Sjöberg, RonaldKTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1j1wpi6 (author)
  • Chang, SarahDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Feng, AllanDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Goldman, Daniel W.Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA (author)
  • Shah, Ami A.Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA (author)
  • Petri, MichelleDepartment of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA (author)
  • Chung, Lorinda S.Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Fiorentino, David F.Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA (author)
  • Käller Lundberg, EmmaKTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Departments of Bioengineering and Pathology, Stanford University, Stanford, CA, USA(Swepub:kth)u12bylj1 (author)
  • Wutz, AntonDepartment of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Honggerberg, Zurich, Switzerland (author)
  • Utz, Paul J.Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA (author)
  • Chang, Howard Y.Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA (author)
  • Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USADepartment of Comparative Medicine, Stanford University, Stanford, CA, USA (creator_code:org_t)

Related titles

  • In:Cell: Elsevier BV187:3, s. 16-7330092-86741097-4172

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