Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome
Abstract Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked b...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-023-00319-z |
| _version_ | 1797388298527703040 |
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| author | Gino Kwon Annika Wiedemann Lisa M. Steinheuer Ana-Luisa Stefanski Franziska Szelinski Tomas Racek Andreas Philipp Frei Klas Hatje Tony Kam-Thong David Schubert Thomas Schindler Thomas Dörner Kevin Thurley |
| author_facet | Gino Kwon Annika Wiedemann Lisa M. Steinheuer Ana-Luisa Stefanski Franziska Szelinski Tomas Racek Andreas Philipp Frei Klas Hatje Tony Kam-Thong David Schubert Thomas Schindler Thomas Dörner Kevin Thurley |
| author_sort | Gino Kwon |
| collection | DOAJ |
| description | Abstract Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked by patient heterogeneity. Here, we performed transcriptional profiling of isolated CD4, CD8, CD16 and CD19 lymphocytes from pSS and SLE patients upon T cell stimulation, in addition to a steady-state condition directly after blood drawing, in total comprising 581 sequencing samples. T cell stimulation, which induced a pronounced inflammatory response in all four cell types, gave rise to substantial re-modulation of lymphocyte subsets in the two autoimmune diseases compared to healthy controls, far exceeding the transcriptomic differences detected at steady-state. In particular, we detected cell-type and disease-specific down-regulation of a range of pro-inflammatory cytokine and chemokine pathways. Such differences between SLE and pSS patients are instrumental for selective immune targeting by future therapies. |
| first_indexed | 2024-03-08T22:37:50Z |
| format | Article |
| id | doaj.art-d842d9b1ede44c8c9b4c539caeb38071 |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-03-08T22:37:50Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-d842d9b1ede44c8c9b4c539caeb380712023-12-17T12:21:27ZengNature Portfolionpj Systems Biology and Applications2056-71892023-12-019111210.1038/s41540-023-00319-zTranscriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndromeGino Kwon0Annika Wiedemann1Lisa M. Steinheuer2Ana-Luisa Stefanski3Franziska Szelinski4Tomas Racek5Andreas Philipp Frei6Klas Hatje7Tony Kam-Thong8David Schubert9Thomas Schindler10Thomas Dörner11Kevin Thurley12Systems Biology of Inflammation, German Rheumatism Research Center, a Leibniz-InstituteRheumatology and Clinical Immunology, Department of Medicine, Charité-Universitätsmedizin BerlinBiomathematics Division, Institute of Experimental Oncology, University Hospital BonnRheumatology and Clinical Immunology, Department of Medicine, Charité-Universitätsmedizin BerlinRheumatology and Clinical Immunology, Department of Medicine, Charité-Universitätsmedizin BerlinRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRoche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRoche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdProduct Development Immunology, F. Hoffmann-La Roche AGRheumatology and Clinical Immunology, Department of Medicine, Charité-Universitätsmedizin BerlinSystems Biology of Inflammation, German Rheumatism Research Center, a Leibniz-InstituteAbstract Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked by patient heterogeneity. Here, we performed transcriptional profiling of isolated CD4, CD8, CD16 and CD19 lymphocytes from pSS and SLE patients upon T cell stimulation, in addition to a steady-state condition directly after blood drawing, in total comprising 581 sequencing samples. T cell stimulation, which induced a pronounced inflammatory response in all four cell types, gave rise to substantial re-modulation of lymphocyte subsets in the two autoimmune diseases compared to healthy controls, far exceeding the transcriptomic differences detected at steady-state. In particular, we detected cell-type and disease-specific down-regulation of a range of pro-inflammatory cytokine and chemokine pathways. Such differences between SLE and pSS patients are instrumental for selective immune targeting by future therapies.https://doi.org/10.1038/s41540-023-00319-z |
| spellingShingle | Gino Kwon Annika Wiedemann Lisa M. Steinheuer Ana-Luisa Stefanski Franziska Szelinski Tomas Racek Andreas Philipp Frei Klas Hatje Tony Kam-Thong David Schubert Thomas Schindler Thomas Dörner Kevin Thurley Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome npj Systems Biology and Applications |
| title | Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome |
| title_full | Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome |
| title_fullStr | Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome |
| title_full_unstemmed | Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome |
| title_short | Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome |
| title_sort | transcriptional profiling upon t cell stimulation reveals down regulation of inflammatory pathways in t and b cells in sle versus sjogren s syndrome |
| url | https://doi.org/10.1038/s41540-023-00319-z |
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