High concentrations of atorvastatin reduce in-vitro function of conventional T and regulatory T cells

Area of Science:

• Immunology
• Pharmacology
• Cellular Biology

Background:

• Regulatory T cells (Tregs) are crucial for immune response regulation and hold therapeutic promise for immune diseases.
• Statins, like atorvastatin (ATV), are known to affect T cell activation and proliferation.
• Previous research suggests statins may enhance Treg frequency and function, but their direct in vitro effects on Treg versus conventional T cell (Tcon) function remain unclear.

Purpose of the Study:

• To simultaneously evaluate the in vitro effects of atorvastatin (ATV) on the functional profile of regulatory T cells (Tregs) and conventional T cells (Tcons).
• To assess ATV's impact on Treg suppressive capacity, T cell activation markers, cytokine production, and calcium flux.

Main Methods:

• Magnetically purified Tcon and Treg subpopulations were co-cultured with CD3/CD28/interleukin-2.
• Cells were treated with atorvastatin (ATV) at 1 µM or 10 µM concentrations.
• Flow cytometry was used to analyze Treg suppressive function, marker expression (FoxP3, CTLA-4, PD-1), activation levels, cytokine production (TNF-α), and calcium flux.

Main Results:

• Atorvastatin (ATV) exhibited no cytotoxic effects on T cells at the tested concentrations.
• 10 µM ATV significantly hampered Treg suppressive capacity and reduced the expression of key Treg markers: FoxP3, CTLA-4, and PD-1.
• This higher ATV concentration also decreased PD-1 and CD45RO expression in Tcons and increased TNF-α production in Tregs, while reducing calcium flux in both cell types, notably in Tcons.

Conclusions:

• High-dose atorvastatin (10 µM) negatively impacts Treg suppressive function, cytokine production, and the expression of Treg-specific markers.
• The study reveals that 10 µM ATV affects cellular functions in both Tregs and Tcons, with a particular emphasis on Treg biology.
• These findings suggest that high-dose statin therapy may have complex immunomodulatory effects that warrant further investigation in the context of immune-related diseases.