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Xist ribonucleoproteins promote female sex-biased autoimmunity

Dou, Diana R. (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Zhao, Yanding (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Belk, Julia A. (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
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Zhao, Yang (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Casey, Kerriann M. (author)
Department of Comparative Medicine, Stanford University, Stanford, CA, USA
Chen, Derek C. (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Li, Rui (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Yu, Bingfei (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Srinivasan, Suhas (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Abe, Brian T. (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Kraft, Katerina (author)
Center for Personal Dynamic Regulomes, Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
Hellström, Cecilia (author)
KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
Sjöberg, Ronald (author)
KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
Chang, Sarah (author)
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
Feng, Allan (author)
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
Goldman, Daniel W. (author)
Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Shah, Ami A. (author)
Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Petri, Michelle (author)
Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Chung, Lorinda S. (author)
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA
Fiorentino, David F. (author)
Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA
Käller Lundberg, Emma (author)
KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Departments of Bioengineering and Pathology, Stanford University, Stanford, CA, USA
Wutz, Anton (author)
Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Honggerberg, Zurich, Switzerland
Utz, Paul J. (author)
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
Chang, Howard Y. (author)
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
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 (creator_code:org_t)
Elsevier BV, 2024
2024
English.
In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 187:3, s. 16-733
Related links:
https://doi.org/10.1...
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https://urn.kb.se/re...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

autoantibody
autoimmunity
long non-coding RNA
RNA binding protein
XIST

Publication and Content Type

ref (subject category)
art (subject category)

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