دورية أكاديمية
Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus
| العنوان: | Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus |
|---|---|
| المؤلفون: | Ukadike, Kennedy C., Najjar, Rayan, Ni, Kathryn, Laine, Amanda, Wang, Xiaoxing, Bays, Alison, Taylor, Martin S., LaCava, John, Mustelin, Tomas |
| المصدر: | Ukadike , K C , Najjar , R , Ni , K , Laine , A , Wang , X , Bays , A , Taylor , M S , LaCava , J & Mustelin , T 2023 , ' Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus ' , Mobile dna , vol. 14 , 5 . https://doi.org/10.1186/s13100-023-00293-7Test |
| سنة النشر: | 2023 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Interferon, L1, Neutrophils, Retrotransposon, Systemic lupus erythematosus |
| الوصف: | Background: Patients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors. Results: L1 ORF1p was detected by flow cytometry primarily in SLE CD66b + CD15 + regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity. Conclusions: We identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/11090579-9929-4daa-a2f1-c03c88b73dc3Test |
| DOI: | 10.1186/s13100-023-00293-7 |
| الإتاحة: | https://doi.org/10.1186/s13100-023-00293-7Test https://hdl.handle.net/11370/11090579-9929-4daa-a2f1-c03c88b73dc3Test https://research.rug.nl/en/publications/11090579-9929-4daa-a2f1-c03c88b73dc3Test https://pure.rug.nl/ws/files/768056476/s13100-023-00293-7.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.8CABA00A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13100-023-00293-7 |
|---|