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Published online: 2024-06-04

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Immune crossroads in atherosclerosis: role of CD8+ T Cells, CD4+ T cells and toll-like receptors in lower extremity arterial disease

Michał Terpiłowski1, Piotr Terlecki1, Stanisław Przywara1, Tomasz Zubilewicz1

Abstract

This review delves into the intricate roles of CD8+ T cells, Th17 cells, regulatory T cells (Tregs), and Toll-like
receptors (TLRs) in the pathogenesis of atherosclerosis, with a particular focus on Lower Extremity Arterial Disease
(LEAD). CD8+ T cells are highlighted for their dual role in atherosclerosis, acting as both exacerbators and
potential protectors within the atherosclerotic environment. Their cytotoxic activity towards cells within plaques
can promote necrotic core formation and plaque instability, while certain subsets, particularly regulatory CD8+
T cells, may exert atheroprotective effects through immunosuppressive functions. Th17 cells, known for their
production of pro-inflammatory cytokines, are implicated in promoting inflammation and disease progression,
suggesting that targeting Th17 cells could be a viable therapeutic strategy. Conversely, Tregs are identified for
their potential to maintain immune balance and prevent excessive inflammatory responses, thereby stabilizing
atherosclerotic lesions. The article also explores the role of TLRs in recognizing pathogen-associated and
damage-associated molecular patterns, triggering inflammatory responses that contribute to atherosclerosis
development and progression. By understanding the complex interplay between these immune components, the
article suggests that modulating the activity of CD8+ T cells, balancing Th17 and Treg responses, and targeting
TLR-mediated signalling pathways could offer new avenues for therapeutic intervention in atherosclerosis and
LEAD. This comprehensive review underscores the need for targeted therapies that can modulate immune
responses, highlighting the potential of immune system targeting in managing atherosclerosis and preventing
LEAD complications.

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