Merck
  • Depletion of Foxp3+ regulatory T cells augments CD4+ T cell immune responses in atherosclerosis-prone hypercholesterolemic mice.

Depletion of Foxp3+ regulatory T cells augments CD4+ T cell immune responses in atherosclerosis-prone hypercholesterolemic mice.

Heliyon (2022-07-29)
Kazuyuki Kasahara, Naoto Sasaki, Hilman Zulkifli Amin, Toru Tanaka, Sayo Horibe, Tomoya Yamashita, Ken-Ichi Hirata, Yoshiyuki Rikitake
摘要

Compelling evidence suggests a crucial role for Foxp3+ regulatory T cells (Tregs) in the control of atherosclerosis. Although suppression of pro-inflammatory CD4+ T cell immune responses is supposed to be important for athero-protective action of Foxp3+ Tregs, few studies have provided direct evidence for this protective mechanism. We investigated the impact of Foxp3+ Treg depletion on CD4+ T cell immune responses and the development of atherosclerosis under hypercholesterolemia. We employed DEREG (depletion of regulatory T cells) mice on an atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr -/-) background, which carry a diphtheria toxin (DT) receptor under the control of the foxp3 gene locus. In these mice, DT injection led to efficient depletion of Foxp3+ Tregs in spleen, lymph nodes and aorta. Depletion of Foxp3+ Tregs augmented CD4+ effector T cell immune responses and aggravated atherosclerosis without affecting plasma lipid profile. Notably, the proportion of pro-inflammatory IFN-γ-producing T cells were increased in spleen and aorta following Foxp3+ Treg depletion, implying that Foxp3+ Tregs efficiently regulate systemic and aortic T cell-mediated inflammatory responses under hypercholesterolemia. Unexpectedly, Foxp3+ Treg depletion resulted in an increase in anti-inflammatory IL-10-producing T cells, which was not sufficient to suppress the augmented proinflammatory T cell immune responses caused by reduced numbers of Foxp3+ Tregs. Our data indicate that Foxp3+ Tregs suppress pro-inflammatory CD4+ T cell immune responses to control atherosclerosis under hypercholesterolemia.

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Sigma-Aldrich
抗-肌动蛋白,α-平滑肌- FITC抗体,小鼠单克隆 小鼠抗, clone 1A4, purified from hybridoma cell culture
Sigma-Aldrich
单克隆抗 FITC-生物素 小鼠抗, clone FL-D6, purified immunoglobulin, buffered aqueous solution