Cell-Specific Transposable Element and Gene Expression Analysis Across Systemic Lupus Erythematosus Phenotypes.

Autor: Cutts Z; University of California, San Francisco, San Francisco., Patterson S; University of California, San Francisco, San Francisco., Maliskova L; University of California, San Francisco, San Francisco., Taylor KE; University of California, San Francisco, San Francisco., Ye CJ; University of California, San Francisco, San Francisco., Dall'Era M; University of California, San Francisco, San Francisco., Yazdany J; University of California, San Francisco, San Francisco., Criswell LA; National Human Genome Research Institute, NIH, Bethesda, Maryland., Fragiadakis GK; University of California, San Francisco, San Francisco., Langelier C; University of California, San Francisco, San Francisco., Capra JA; University of California, San Francisco, San Francisco., Sirota M; University of California, San Francisco, San Francisco., Lanata CM; National Human Genome Research Institute, NIH, Bethesda, Maryland.
Jazyk: angličtina
Zdroj: ACR open rheumatology [ACR Open Rheumatol] 2024 Aug 14. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1002/acr2.11713
Abstrakt: Objective: There is an established yet unexplained link between interferon (IFN) and systemic lupus erythematosus (SLE). The expression of sequences derived from transposable elements (TEs) may contribute to SLE phenotypes, specifically production of type I IFNs and generation of autoantibodies.
Methods: We profiled cell-sorted RNA-sequencing data (CD4 + T cells, CD14 + monocytes, CD19 + B cells, and natural killer cells) from peripheral blood mononuclear cells of 120 patients with SLE and quantified TE expression identifying 27,135 TEs. We tested for differential TE expression across 10 SLE phenotypes, including autoantibody production and disease activity.
Results: We found 731 differentially expressed (DE) TEs across all SLE phenotypes that were mostly cell specific and phenotype specific. DE TEs were enriched for specific families and open reading frames of viral genes encoded in TE sequences. Increased expression of DE TEs was associated with genes involved in antiviral activity, such as LY6E, ISG15, and TRIM22, and pathways such as IFN signaling.
Conclusion: These findings suggest that expression of TEs contributes to activation of SLE-related mechanisms in a cell-specific manner, which can impact disease diagnostics and therapeutics.
(© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
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