4.7 Article

Follicular regulatory helper T cells control the response of regulatory B cells to a high-cholesterol diet

Journal

CARDIOVASCULAR RESEARCH
Volume 117, Issue 3, Pages 743-755

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvaa069

Keywords

Follicular helper cell (T-FH); Follicular regulatory helper T cells (T-FR); Regulatory B cell; Lymphangiogenesis; Atherosclerosis

Funding

  1. European Commission [FP7-INNOVATION I HEALTH-F2-2013-602114]
  2. Swiss National Science Foundation [310030_152912/1]
  3. Geneva Private Foundation
  4. Swiss National Science Foundation (SNF) [310030_152912] Funding Source: Swiss National Science Foundation (SNF)

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The study shows that follicular regulatory helper T cells (T-FR) can control regulatory B cell (B-REG) populations in mice models on a high-cholesterol diet, leading to the suppression of proatherogenic processes. This suggests that T-FR cells may have atheroprotective effects by modulating immune processes related to atherosclerosis.
Aims B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified. Methods and results In this study, we show that follicular regulatory helper T cells (T-FR) control regulatory B cell (B-REG) populations in Apoe(-/)(-) mice models on a high-cholesterol diet (HCD). Feeding mice with HCD resulted in up-regulation of T-FR and B-REG cell populations, causing the suppression of proatherogenic follicular helper T cell (T-FH) response. T-FH cell modulation is correlated with the growth of atherosclerotic plaque size in thoracoabdominal aortas and aortic root plaques, suggesting that T-FR cells are atheroprotective. During adoptive transfer experiments, T-FR cells transferred into HCD mice decreased T-FH cell populations, atherosclerotic plaque size, while B-REG cell population and lymphangiogenesis are significantly increased. Conclusion Our results demonstrate that, through different strategies, both T-FR and T-FH cells modulate anti- and proatherosclerotic immune processes in an Apoe(-/-) mice model since T-FR cells are able to regulate both T-FH and B-REG cell populations as well as lymphangiogenesis and lipoprotein metabolism. [GRAPHICS] .

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