Introduction
Coronary artery disease (CAD), primarily caused by atherosclerosis, is the third leading cause of mortality worldwide and is associated with 17.8 million deaths annually.[1]
Atherosclerosis is characterized by the build-up of plaques in the coronary arteries, leading to restricted blood flow to the heart.
The immune system plays a critical role in both the development and prevention of these plaques. Specifically, the inflammatory response driven by various immune cells triggers pathways that result in plaque formation.
Accumulation of low-density lipoprotein (LDL) damages the arterial intima, attracting neutrophils, macrophages, and lymphocytes, which initiate a pro-inflammatory cascade leading to plaque development.[2]
However, regulatory T cells (Tregs) can mitigate these pro-inflammatory responses, presenting a potential avenue for CAD immunotherapy.
The Role of Regulatory T Cells (Tregs) in Combating Atherosclerosis
Regulatory T cells are crucial in suppressing the proliferation and cytokine release of cytotoxic T-cells. They also modulate the activity of other immune cells, including natural killer cells, dendritic cells, and B cells.
Tregs exhibit anti-atherosclerotic effects primarily through the production of interleukin (IL)-10, an anti-inflammatory cytokine, and by inducing macrophage differentiation into an anti-inflammatory subtype.[3]
One significant event in atherosclerosis is the transformation of macrophages into foam cells. Tregs can prevent foam cell formation by inhibiting lipid accumulation in macrophages.
Additionally, Tregs help reduce LDL levels and influence cholesterol metabolism. In Treg-deficient mouse models, plasma cholesterol levels rise, and atherosclerosis progression accelerates.
Conversely, adoptive transfer of CD4+CD25+ Tregs in mice reduces atherosclerotic plaque formation. These findings suggest that expanding Tregs in vivo or ex vivo could lead to therapies capable of halting atherosclerosis progression.
Advances in Treg-Based Immunotherapies
Research has explored various in vivo treatments to increase Treg numbers. One study involved administering an IL-2/anti-IL-2 complex to LDL receptor knock-out mice on a Western-type diet.[4]
This approach significantly expanded IL-10 producing Tregs in the peripheral blood and lymphoid organs, leading to a reduction in atherosclerotic plaque formation and increased stability of preexisting plaque lesions.
Tolerogenic Dendritic Cells: A Promising Therapeutic Approach
Inducing a tolerogenic dendritic cell (DC) phenotype has also been studied for its potential in treating atherosclerosis.
Culturing DCs with IL-10 and atherosclerosis-related antigens led to the induction of tolerogenic DCs. Adoptive transfer of these cells in mice activated Tregs, resulting in anti-atherosclerotic effects.
This approach underscores the potential of leveraging the immune system to combat CAD.
Future Directions and Implications for Cardiovascular Health
The immune system’s involvement in atherosclerosis pathogenesis highlights its potential as a target for innovative CAD therapies.
Ongoing studies aim to better understand the role of immune cells in CAD and develop effective immunotherapies.
Harnessing the power of Tregs and tolerogenic DCs could revolutionize the prevention and treatment of cardiovascular diseases, offering hope for millions worldwide.
Stay Informed with Cytologics
At Cytologics, we are at the forefront of research in immunotherapy for coronary artery disease.
Transform your understanding of coronary artery disease with the latest insights from Cytologics.
Subscribe to our newsletter now for updates on groundbreaking research and innovative treatments.
References
[1] Brown JC, Gerhardt TE, Kwon E. Risk Factors for Coronary Artery Disease. [Updated 2023 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554410/
[2] Mehu M, Narasimhulu CA, Singla DK. Inflammatory Cells in Atherosclerosis. Antioxidants (Basel). 2022 Jan 26;11(2):233. doi: 10.3390/antiox11020233. PMID: 35204116; PMCID: PMC8868126. Available from: https://www.mdpi.com/2076-3921/11/2/233.
[3] Kong, P., Cui, ZY., Huang, XF. et al. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Sig Transduct Target Ther 7, 131 (2022). https://doi.org/10.1038/s41392-022-00955-7. Available from: https://www.nature.com/articles/s41392-022-00955-7.
[4] Zhang H, Xia Y, Ye Q, Yu F, Zhu W, Li P, Wei Z, Yang Y, Shi Y, Thomson AW, Chen J, Hu X. In Vivo Expansion of Regulatory T Cells with IL-2/IL-2 Antibody Complex Protects against Transient Ischemic Stroke. J Neurosci. 2018 Nov 21;38(47):10168-10179. doi: 10.1523/JNEUROSCI.3411-17.2018. Epub 2018 Oct 5. PMID: 30291203; PMCID: PMC6246882.
