Open AccessEffects of Atorvastatin on T‐Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C‐Reactive Protein and Interleukin 6
Author(s) -
Sun Jitong,
Kumar Panda Pritam,
Kumar Samal Shailesh,
Ahuja Rajeev,
Ajeganova Sofia,
Hafström Ingiäld,
Liu Anquan,
Frostegård Johan
Publication year - 2021
Publication title -
acr open rheumatology
Language(s) - English
Resource type - Journals
ISSN - 2578-5745
DOI - 10.1002/acr2.11305
Subject(s) - atorvastatin , apoptosis , foxp3 , interleukin , fas receptor , immunology , rar related orphan receptor gamma , il 2 receptor , t cell , chemistry , medicine , endocrinology , programmed cell death , cytokine , immune system , biochemistry
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 + CD127 dim/− ) 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.