Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

Abstract

Aims CD8+ T-cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces IL-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis. Methods and Results Flow cytometry analysis of atherosclerotic lesions from apoE-/- mice revealed a pronounced increase in RORγt+CD8+ T-cells compared to the spleen, indicating a lesion-specific increase in Tc17 cells. To study whether and how the Tc17 subset affects atherosclerosis, we performed an adoptive transfer of Tc17 cells or undifferentiated Tc0 cells into CD8-/-LDLr-/- mice fed a Western-type diet. Using flow cytometry, we showed that Tc17 cells retained a high level of IL-17A production in vivo. Moreover, Tc17 cells produced lower levels of IFN-γ than their Tc0 counterparts. Analysis of the aortic root revealed that the transfer of Tc17 cells did not increase atherosclerotic lesion size, in contrast to Tc0-treated mice. Conclusion These findings demonstrate a lesion-localized increase in Tc17 cells in an atherosclerotic mouse model. Tc17 cells appeared to be non-atherogenic, in contrast to their Tc0 counterpart. Translational perspective CD8+ T-cells are present in high numbers in human atherosclerotic plaques, however their role in inflammation and the pathogenesis of atherosclerosis remains elusive. Our results indicate that the majority of CD8+ T-cells in atherosclerotic plaques of mice have lost their ability to produce the pro-inflammatory cytokine IFN-γ and gain traits of IL-17-producing CD8+ T-cells (Tc17 cells). We show that this subset of CD8+ T-cells is less atherogenic then IFN-γ producing Tc1 cells.

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

“… 39 Moreover, in vitro studies show that IL-17 can induce and stimulate the cells involved in atherosclerosis (macrophages, dendritic cells, vascular smooth muscle cells), thus causing inflammatory damage and apoptosis. 36 , 38 Our results confirm these immune-related pathways are closely related to CAD, indicating their importance. However, the specific mechanisms by which these immune pathways and their involved inflammatory cytokines and chemokines participate in the occurrence of CAD still need further research.…”

“… 35 , 36 Th2 cells can antagonize atherosclerosis by secreting interleukin (IL)-4 and IL-10. 37 , 38 The proportions of Th17 and its secreted IL-17 in CAD and atherosclerosis are increased, and positively correlated with the severity of the disease. 34 Previous clinical studies have found that the expression of Th17 and IL-17 in peripheral blood of patients with acute coronary syndrome is increased compared with patients with stable angina pectoris and chest pain syndrome.…”

Targeting gut microbiota and immune crosstalk: potential mechanisms of natural products in the treatment of atherosclerosis

“…In addition, CD8 + T cells can differentiate into subpopulations with specific cytokine profiles. CD8 + Tc17 T cells do not affect the development of early AS although they accumulate in the lesioned areas of mice with AS ( van Duijn et al, 2021 ). In contrast, CD8 + IFN-γ + T cells mediate the upregulation of immune responses and secretion of pro-inflammatory cytokines during the progressive phase of AS, exacerbating AS load and promoting the inflammatory response ( Li et al, 2023 ).…”