دورية أكاديمية
Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus [version 1; peer review: 1 approved, 2 approved with reservations]
| العنوان: | Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus [version 1; peer review: 1 approved, 2 approved with reservations] |
|---|---|
| المؤلفون: | Dominik Trzupek, Fiona Hamey, Mercede Lee, John A. Todd, Linda S. Wicker, Ricardo C. Ferreira |
| المصدر: | Wellcome Open Research, Vol 6 (2021) |
| بيانات النشر: | Wellcome, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Single-cell RNA-sequencing (scRNA-seq), multi-omics, BD Rhapsody, AbSeq, cytotoxic CD4+ T cells (CTLs), systemic lupus erythematosus (SLE), eng, Medicine, Science |
| الوصف: | Background: The characterisation of the peripheral immune system in the autoimmune disease systemic lupus erythematosus (SLE) at the single-cell level has been limited by the reduced sensitivity of current whole-transcriptomic technologies. Here we employ a targeted single-cell multi-omics approach, combining protein and mRNA quantification, to generate a high-resolution map of the T lymphocyte and natural killer (NK) cell populations in blood from SLE patients. Methods: We designed a custom panel to quantify the transcription of 534 genes in parallel with the expression of 51 surface protein targets using the BD Rhapsody AbSeq single-cell system. We applied this technology to profile 20,656 T and NK cells isolated from peripheral blood from an SLE patient with a type I interferon (IFN)-induced gene expression signature (IFNhi), and an age- and sex- matched IFNlow SLE patient and healthy donor. Results: We confirmed the presence of a rare cytotoxic CD4+ T cell (CTL) subset, which was exclusively present in the IFNhi patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57+ CD8+ T cell and CD16+ NKdim phenotypes, and the presence of a subset of recently-activated naïve CD4+ T cells. Conclusions: Our results identify IFN-driven changes in the composition and phenotype of T and NK cells that are consistent with a systemic immune activation within the IFNhi patient, and underscore the added resolving power of this multi-omics approach to identify rare immune subsets. Consequently, we were able to find evidence for novel cellular peripheral biomarkers of SLE disease activity, including a subpopulation of CD57+ CD4+ CTLs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2398-502X |
| Relation: | https://wellcomeopenresearch.org/articles/6-149/v1; https://doaj.org/toc/2398-502X |
| DOI: | 10.12688/wellcomeopenres.16883.1 |
| URL الوصول: | https://doaj.org/article/6f7b8027351748d68ec660fd13021b07 |
| رقم الأكسشن: | edsdoj.6f7b8027351748d68ec660fd13021b07 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2398502X |
|---|---|
| DOI: | 10.12688/wellcomeopenres.16883.1 |