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Updated: Jun 3, 2026
The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Calcium signaling in systemic lupus erythematosus T cells: a treatment target
Vasileios C Kyttaris1, Zheng Zhang, Ourania Kampagianni
1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. vkyttari@bidmc.harvard.edu
Objective:
Systemic lupus erythematosus (SLE) T cells display a hyperactive calcineurin/NF-AT pathway. The aim of this study was to determine whether this pathway is responsible for the aberrant SLE T cell function and to test the effectiveness of the recently recognized calcineurin inhibitor dipyridamole in limiting SLE-related pathology.
Methods:
T cells and mononuclear cells were isolated from the peripheral blood of SLE patients and healthy individuals. Murine cells were isolated from the spleens and lymph nodes of lupus-prone MRL/lpr mice and control MRL/MpJ mice. Cells were treated in vitro with tacrolimus, dipyridamole, or control. MRL/lpr mice were injected intraperitoneally with 50 mg/kg of dipyridamole 3 times a week for 3 weeks.
Results:
MRL/lpr T cells, especially CD3+CD4-CD8- cells, displayed a robust calcium influx upon activation and increased levels of NF-ATc1. MRL/lpr T cells (both CD4+ and CD3+CD4-CD8- cells) provided help to B cells to produce immunoglobulin in a calcineurin-dependent manner. Dipyridamole treatment of SLE T cells significantly inhibited CD154 expression, interferon-γ, interleukin-17 (IL-17), and IL-6 production, and T cell-dependent B cell immunoglobulin secretion. Treatment of MRL/lpr mice with dipyridamole alleviated lupus nephritis and prevented the appearance of skin ulcers.
Conclusion:
NF-AT activation is a key step in the activation of SLE T cells and the production of immunoglobulin. Dipyridamole inhibits SLE T cell function and improves pathologic changes of the disease in lupus-prone mice. We propose that dipyridamole can be used in treatment regimens for patients with SLE.
Insights
Systemic lupus erythematosus (SLE) T cells show hyperactive pathways. Dipyridamole effectively inhibits SLE T cell function and reduces disease pathology in mice, suggesting its therapeutic potential.
Area of Science:
- Immunology
- Rheumatology
Background:
- Systemic lupus erythematosus (SLE) is characterized by aberrant T cell hyperactivity.
- The calcineurin/NF-AT pathway is hyperactive in SLE T cells, contributing to disease pathogenesis.
Purpose of the Study:
- To investigate the role of the calcineurin/NF-AT pathway in SLE T cell dysfunction.
- To evaluate dipyridamole, a calcineurin inhibitor, for its efficacy in treating SLE-related pathology.
Main Methods:
- Isolation of T cells and mononuclear cells from SLE patients and lupus-prone mice.
- In vitro treatment of cells with tacrolimus or dipyridamole.
- In vivo administration of dipyridamole to MRL/lpr mice.
Main Results:
- SLE T cells exhibit increased calcium influx and NF-ATc1 levels.
- Dipyridamole treatment suppressed key inflammatory markers (IFN-γ, IL-17, IL-6) and immunoglobulin production.
- Dipyridamole treatment alleviated lupus nephritis and skin ulcers in MRL/lpr mice.
Conclusions:
- NF-AT activation is crucial for SLE T cell activation and immunoglobulin production.
- Dipyridamole demonstrates significant potential in inhibiting SLE T cell function and ameliorating disease manifestations.
- Dipyridamole warrants consideration as a therapeutic agent for SLE patients.
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