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

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• A known association exists between interferon (IFN) and systemic lupus erythematosus (SLE), but the underlying mechanisms remain unclear.
• Transposable elements (TEs) are DNA sequences that can change their position within a genome, and their expression has been implicated in autoimmune diseases.
• TE expression may contribute to SLE phenotypes, including the production of type I interferons and autoantibodies.

Purpose of the Study:

• To investigate the role of transposable element (TE) expression in the pathogenesis of systemic lupus erythematosus (SLE).
• To identify specific TEs and their expression patterns in different immune cell types from SLE patients.
• To correlate TE expression with distinct SLE phenotypes, such as autoantibody production and disease activity.

Main Methods:

• RNA-sequencing was performed on sorted immune cells (CD4+ T cells, CD14+ monocytes, CD19+ B cells, NK cells) from 120 SLE patients.
• Quantification of transposable element (TE) expression identified 27,135 TEs.
• Differential TE expression was analyzed across 10 SLE phenotypes, including autoantibody status and disease activity metrics.

Main Results:

• 731 differentially expressed (DE) TEs were identified across SLE phenotypes, showing cell- and phenotype-specific patterns.
• DE TEs were enriched in families and open reading frames associated with viral genes.
• Increased DE TE expression correlated with genes and pathways involved in antiviral responses and interferon signaling (e.g., LY6E, ISG15, TRIM22).

Conclusions:

• Transposable element (TE) expression contributes to the activation of SLE-related immune mechanisms in a cell-specific manner.
• These findings highlight the potential of TEs as biomarkers for SLE diagnostics.
• Targeting TE expression could offer novel therapeutic strategies for systemic lupus erythematosus.