Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6
Objective We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. Methods Mononuclear cell...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11305 |
| _version_ | 1819115667552468992 |
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| author | Jitong Sun Pritam Kumar Panda Shailesh Kumar Samal Rajeev Ahuja Sofia Ajeganova Ingiäld Hafström Anquan Liu Johan Frostegård |
| author_facet | Jitong Sun Pritam Kumar Panda Shailesh Kumar Samal Rajeev Ahuja Sofia Ajeganova Ingiäld Hafström Anquan Liu Johan Frostegård |
| author_sort | Jitong Sun |
| collection | DOAJ |
| description | Objective We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. Methods Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction. Cytokines in plasma were determined by enzyme‐linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin. Results Among patients with SLE, the proportion of Th17 (CD4+IL17+) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4+CD25+CD127dim/−) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL‐6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C‐reactive protein (CRP) and also significantly with IL‐6. Conclusion There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95‐induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL‐6, implying a novel role of atorvastatin. |
| first_indexed | 2024-12-22T05:04:50Z |
| format | Article |
| id | doaj.art-c29b209673f342b68a0e5abcec80a969 |
| institution | Directory Open Access Journal |
| issn | 2578-5745 |
| language | English |
| last_indexed | 2024-12-22T05:04:50Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj.art-c29b209673f342b68a0e5abcec80a9692022-12-21T18:38:08ZengWileyACR Open Rheumatology2578-57452021-09-013964265310.1002/acr2.11305Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6Jitong Sun0Pritam Kumar Panda1Shailesh Kumar Samal2Rajeev Ahuja3Sofia Ajeganova4Ingiäld Hafström5Anquan Liu6Johan Frostegård7Karolinska Institutet Stockholm SwedenUppsala University Uppsala SwedenKarolinska Institutet Stockholm SwedenUppsala University and Royal Institute of Technology Stockholm SwedenKarolinska Institutet, Stockholm, Sweden, and Universitair Ziekenhuis BrusselVrije Universiteit Brussel Brussels BelgiumKarolinska Institutet and Karolinska University Hospital Stockholm SwedenKarolinska Institutet Stockholm SwedenKarolinska Institutet Stockholm SwedenObjective We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds. Methods Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real‐time reverse transcription–polymerase chain reaction. Cytokines in plasma were determined by enzyme‐linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin. Results Among patients with SLE, the proportion of Th17 (CD4+IL17+) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4+CD25+CD127dim/−) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL‐6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C‐reactive protein (CRP) and also significantly with IL‐6. Conclusion There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95‐induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL‐6, implying a novel role of atorvastatin.https://doi.org/10.1002/acr2.11305 |
| spellingShingle | Jitong Sun Pritam Kumar Panda Shailesh Kumar Samal Rajeev Ahuja Sofia Ajeganova Ingiäld Hafström Anquan Liu Johan Frostegård Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 ACR Open Rheumatology |
| title | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
| title_full | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
| title_fullStr | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
| title_full_unstemmed | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
| title_short | Effects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6 |
| title_sort | effects of atorvastatin on t cell activation and apoptosis in systemic lupus erythematosus and novel simulated interactions with c reactive protein and interleukin 6 |
| url | https://doi.org/10.1002/acr2.11305 |
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