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]
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,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wellcome
2021-06-01
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| Series: | Wellcome Open Research |
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| Online Access: | https://wellcomeopenresearch.org/articles/6-149/v1 |
| _version_ | 1811246660409360384 |
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| author | Dominik Trzupek Fiona Hamey Mercede Lee John A. Todd Linda S. Wicker Ricardo C. Ferreira |
| author_facet | Dominik Trzupek Fiona Hamey Mercede Lee John A. Todd Linda S. Wicker Ricardo C. Ferreira |
| author_sort | Dominik Trzupek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T14:56:06Z |
| format | Article |
| id | doaj.art-6f7b8027351748d68ec660fd13021b07 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-04-12T14:56:06Z |
| publishDate | 2021-06-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-6f7b8027351748d68ec660fd13021b072022-12-22T03:28:13ZengWellcomeWellcome Open Research2398-502X2021-06-01618624Single-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]Dominik Trzupek0Fiona Hamey1Mercede Lee2John A. Todd3https://orcid.org/0000-0003-2740-8148Linda S. Wicker4Ricardo C. Ferreira5https://orcid.org/0000-0001-5733-3285JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKJDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKJDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKJDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKJDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKJDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UKBackground: 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.https://wellcomeopenresearch.org/articles/6-149/v1Single-cell RNA-sequencing (scRNA-seq) multi-omics BD Rhapsody AbSeq cytotoxic CD4+ T cells (CTLs) systemic lupus erythematosus (SLE)eng |
| spellingShingle | Dominik Trzupek Fiona Hamey Mercede Lee John A. Todd Linda S. Wicker Ricardo C. Ferreira 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] Wellcome Open Research Single-cell RNA-sequencing (scRNA-seq) multi-omics BD Rhapsody AbSeq cytotoxic CD4+ T cells (CTLs) systemic lupus erythematosus (SLE) eng |
| title | 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] |
| title_full | 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] |
| title_fullStr | 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] |
| title_full_unstemmed | 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] |
| title_short | 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] |
| title_sort | 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 |
| topic | Single-cell RNA-sequencing (scRNA-seq) multi-omics BD Rhapsody AbSeq cytotoxic CD4+ T cells (CTLs) systemic lupus erythematosus (SLE) eng |
| url | https://wellcomeopenresearch.org/articles/6-149/v1 |
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