Depletion of Foxp3+ regulatory T cells augments CD4+ T cell immune responses in atherosclerosis-prone hypercholesterolemic mice. Issue 7 (July 2022)

• Record Type: Journal Article
• Authors: Kasahara, Kazuyuki; Sasaki, Naoto; Amin, Hilman Zulkifli; Tanaka, Toru; Horibe, Sayo; Yamashita, Tomoya; Hirata, Ken-ichi; Rikitake, Yoshiyuki
• Is Part Of: Heliyon. Volume 8:Issue 7(2022)
• Publication Date: 2022-07
• Subjects: Atherosclerosis -- Immunology -- Regulatory T cells -- CD4+ T cells -- Inflammation; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2022.e09981
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: 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. Abstract : Atherosclerosis; Immunology; Regulatory T cells, CD4 + T cells; inflammation.