Interferons and Cytokines Induce Transcriptional Activation of the Long-Interspersed Element-1 in Myeloid Cells from Autoimmune Patients.

Approximately 17% of our genome consists of copies of the retrotransposon "long interspersed element-1" (LINE-1 or L1). Patients with systemic lupus erythematosus (SLE) frequently have autoantibodies against the L1-encoded ORF1 protein (ORF1p), which correlate with disease activity and interferon gene signature. ORF1p is present in neutrophils from patients with active disease in perinuclear ribonucleoprotein particles that also contain Ro60 and nucleic acid sensors.

Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.

Long-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune cells. We used a comprehensive and unbiased approach to investigate the role of ACSL1 induction by interferon type I (IFN-I) in myeloid cells in vitro and in a mouse model of IFN-I overproduction.